Receptors, Opioid, kappa: A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.Receptors, Opioid: Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Receptors, Opioid, delta: A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.Analgesics, Opioid: Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Dynorphins: A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters.Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.Enkephalin, D-Penicillamine (2,5)-: A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.Enkephalin, Ala(2)-MePhe(4)-Gly(5)-: An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the ENKEPHALINS, the DYNORPHINS, and the ENDORPHINS. Each of these families derives from different precursors, proenkephalin, prodynorphin, and PRO-OPIOMELANOCORTIN, respectively. There are also at least three classes of OPIOID RECEPTORS, but the peptide families do not map to the receptors in a simple way.Benzeneacetamides: Compounds based on benzeneacetamide, that are similar in structure to ACETANILIDES.Diprenorphine: A narcotic antagonist similar in action to NALOXONE. It is used to remobilize animals after ETORPHINE neuroleptanalgesia and is considered a specific antagonist to etorphine.Morphinans: Compounds based on a partially saturated iminoethanophenanthrene, which can be described as ethylimino-bridged benzo-decahydronaphthalenes. They include some of the OPIOIDS found in PAPAVER that are used as ANALGESICS.Ethylketocyclazocine: A kappa opioid receptor agonist. The compound has analgesic action and shows positive inotropic effects on the electrically stimulated left atrium. It also affects various types of behavior in mammals such as locomotion, rearing, and grooming.PyrrolidinesEnkephalin, Leucine: One of the endogenous pentapeptides with morphine-like activity. It differs from MET-ENKEPHALIN in the LEUCINE at position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Enkephalin, Leucine-2-Alanine: A delta-selective opioid (ANALGESICS, OPIOID). It can cause transient depression of mean arterial blood pressure and heart rate.Narcotics: Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS.Benzomorphans: Morphine derivatives of the methanobenzazocine family that act as potent analgesics.Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.Cyclazocine: An analgesic with mixed narcotic agonist-antagonist properties.Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the PRO-OPIOMELANOCORTIN precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; OPIOID PEPTIDES is used for the broader group.Etorphine: A narcotic analgesic morphinan used as a sedative in veterinary practice.Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain.Diterpenes, Clerodane: A group of DITERPENES cyclized into 2-rings with a side-chain.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Opioid-Related Disorders: Disorders related or resulting from abuse or mis-use of opioids.beta-Endorphin: A 31-amino acid peptide that is the C-terminal fragment of BETA-LIPOTROPIN. It acts on OPIOID RECEPTORS and is an analgesic. Its first four amino acids at the N-terminal are identical to the tetrapeptide sequence of METHIONINE ENKEPHALIN and LEUCINE ENKEPHALIN.Immunoglobulin kappa-Chains: One of the types of light chains of the immunoglobulins with a molecular weight of approximately 22 kDa.Dynamin I: A subtype of dynamin found primarily in the NEURONS of the brain.Analgesics, Non-Narcotic: A subclass of analgesic agents that typically do not bind to OPIOID RECEPTORS and are not addictive. Many non-narcotic analgesics are offered as NONPRESCRIPTION DRUGS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Buprenorphine: A derivative of the opioid alkaloid THEBAINE that is a more potent and longer lasting analgesic than MORPHINE. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use.Pain: An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Fentanyl: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078)Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Pain Measurement: Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Benzylidene Compounds: Compounds containing the PhCH= radical.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Analgesia: Methods of PAIN relief that may be used with or in place of ANALGESICS.Oligopeptides: Peptides composed of between two and twelve amino acids.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Guanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Morphine Derivatives: Analogs or derivatives of morphine.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Heroin: A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed)Enkephalin, Methionine: One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.Methadone: A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Substance Withdrawal Syndrome: Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Kinetics: The rate dynamics in chemical or physical systems.Morphine Dependence: Strong dependence, both physiological and emotional, upon morphine.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Hydromorphone: An opioid analgesic made from MORPHINE and used mainly as an analgesic. It has a shorter duration of action than morphine.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Periaqueductal Gray: Central gray matter surrounding the CEREBRAL AQUEDUCT in the MESENCEPHALON. Physiologically it is probably involved in RAGE reactions, the LORDOSIS REFLEX; FEEDING responses, bladder tonus, and pain.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes.Hyperalgesia: An increased sensation of pain or discomfort produced by mimimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve.Loperamide: One of the long-acting synthetic ANTIDIARRHEALS; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.Pain Threshold: Amount of stimulation required before the sensation of pain is experienced.Somatostatin: A 14-amino acid peptide named for its ability to inhibit pituitary GROWTH HORMONE release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of THYROID-STIMULATING HORMONE; PROLACTIN; INSULIN; and GLUCAGON besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, SRIF-28 with a 14-amino acid extension at the N-terminal.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Salvia: A genus in the mint family (LAMIACEAE).Immunoglobulin Light Chains: Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule.NF-kappa B: Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.Nociceptors: Peripheral AFFERENT NEURONS which are sensitive to injuries or pain, usually caused by extreme thermal exposures, mechanical forces, or other noxious stimuli. Their cell bodies reside in the DORSAL ROOT GANGLIA. Their peripheral terminals (NERVE ENDINGS) innervate target tissues and transduce noxious stimuli via axons to the CENTRAL NERVOUS SYSTEM.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Cricetulus: A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.Spinal Cord: A cylindrical column of tissue that lies within the vertebral canal. It is composed of WHITE MATTER and GRAY MATTER.Opiate Alkaloids: Alkaloids found in OPIUM from PAPAVER that induce analgesic and narcotic effects by action upon OPIOID RECEPTORS.AzocinesDrug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Spiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Heroin Dependence: Strong dependence, both physiological and emotional, upon heroin.Injections, Intraventricular: Injections into the cerebral ventricles.D-Ala(2),MePhe(4),Met(0)-ol-enkephalin: A stable synthetic analog of methionine enkephalin (ENKEPHALIN, METHIONINE). Actions are similar to those of methionine enkephalin. Its effects can be reversed by narcotic antagonists such as naloxone.Gene Rearrangement, B-Lymphocyte, Light Chain: Ordered rearrangement of B-lymphocyte variable gene regions coding for the kappa or lambda IMMUNOGLOBULIN LIGHT CHAINS, thereby contributing to antibody diversity. It occurs during the second stage of differentiation of the IMMATURE B-LYMPHOCYTES.Nalbuphine: A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors.Piperidines: A family of hexahydropyridines.Behavior, Animal: The observable response an animal makes to any situation.Chronic Pain: Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain.Immunoglobulin lambda-Chains: One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Dihydromorphine: A semisynthetic analgesic used in the study of narcotic receptors.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Opiate Substitution Treatment: Medical treatment for opioid dependence using a substitute opiate such as METHADONE or BUPRENORPHINE.I-kappa B Proteins: A family of inhibitory proteins which bind to the REL PROTO-ONCOGENE PROTEINS and modulate their activity. In the CYTOPLASM, I-kappa B proteins bind to the transcription factor NF-KAPPA B. Cell stimulation causes its dissociation and translocation of active NF-kappa B to the nucleus.G-Protein-Coupled Receptor Kinase 3: A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Oxymorphone: An opioid analgesic with actions and uses similar to those of MORPHINE, apart from an absence of cough suppressant activity. It is used in the treatment of moderate to severe pain, including pain in obstetrics. It may also be used as an adjunct to anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1092)Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Arrestins: Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.Vas Deferens: The excretory duct of the testes that carries SPERMATOZOA. It rises from the SCROTUM and joins the SEMINAL VESICLES to form the ejaculatory duct.Immunoglobulin Variable Region: That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Cyclic AMP: An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC 4.6.1.1.Protein PrecursorsPrescription Drug Misuse: Improper use of drugs or medications outside the intended purpose, scope, or guidelines for use. This is in contrast to MEDICATION ADHERENCE, and distinguished from DRUG ABUSE, which is a deliberate or willful action.Ileum: The distal and narrowest portion of the SMALL INTESTINE, between the JEJUNUM and the ILEOCECAL VALVE of the LARGE INTESTINE.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Hydrocodone: Narcotic analgesic related to CODEINE, but more potent and more addicting by weight. It is used also as cough suppressant.Nociception: Sensing of noxious mechanical, thermal or chemical stimuli by NOCICEPTORS. It is the sensory component of visceral and tissue pain (NOCICEPTIVE PAIN).Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Tetrahydroisoquinolines: A group of ISOQUINOLINES in which the nitrogen containing ring is protonated. They derive from the non-enzymatic Pictet-Spengler condensation of CATECHOLAMINES with ALDEHYDES.Conditioning, Operant: Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced.Drug Overdose: Accidental or deliberate use of a medication or street drug in excess of normal dosage.Mice, Inbred ICRPertussis Toxin: One of the virulence factors produced by BORDETELLA PERTUSSIS. It is a multimeric protein composed of five subunits S1 - S5. S1 contains mono ADPribose transferase activity.Prescription Drugs: Drugs that cannot be sold legally without a prescription.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Electroacupuncture: A form of acupuncture with electrical impulses passing through the needles to stimulate NERVE TISSUE. It can be used for ANALGESIA; ANESTHESIA; REHABILITATION; and treatment for diseases.PiperazinesSufentanil: An opioid analgesic that is used as an adjunct in anesthesia, in balanced anesthesia, and as a primary anesthetic agent.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Pentazocine: The first mixed agonist-antagonist analgesic to be marketed. It is an agonist at the kappa and sigma opioid receptors and has a weak antagonist action at the mu receptor. (From AMA Drug Evaluations Annual, 1991, p97)Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Benzamides: BENZOIC ACID amides.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Meptazinol: A narcotic antagonist with analgesic properties. It is used for the control of moderate to severe pain.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.

*Dynorphin A

... and delta-opioid receptors; it has the highest binding affinity for the kappa-opioid receptor. Dynorphin 1-13 - Compound ... Dynorphin A is a form of dynorphin and an endogenous opioid peptide with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg- ... Dynorphin A1-8 is an agonist at the mu-, kappa-, ...

*AT-076

... which increased affinity for the nociceptin receptor by 10-fold and for the μ- and δ-opioid receptors by 3-6-fold. Cebranopadol ... "Discovery of the First Small-Molecule Opioid Pan Antagonist with Nanomolar Affinity at Mu, Delta, Kappa, and Nociceptin Opioid ... and δ-opioid receptor (Ki = 19.6 nM) and as a noncompetitive antagonist of the κ-opioid receptor (Ki = 1.14 nM) and nociceptin ... It acts as a silent antagonist of all four of the opioid receptors, behaving as a competitive antagonist of the μ-opioid ...

*JDTic

"Discovery of the First Small-Molecule Opioid Pan Antagonist with Nanomolar Affinity at Mu, Delta, Kappa, and Nociceptin Opioid ... and is highly selective for the KOR over the μ-opioid receptor (MOR), δ-opioid receptor (DOR), and nociceptin receptor (NOP). ... and the presence of kappa receptors and dynorphin in cardiac tissue. Given the potentially serious clinical consequences of VT ... "Synthesis and in vitro Opioid Receptor Functional Antagonism of Analogues of the Selective κ Opioid Receptor Antagonist (3R)-7- ...

*MCOPPB

It has only moderate affinity for the mu opioid receptor, weak affinity for the kappa opioid receptor and negligible binding at ... with a pKi of 10.07 and much weaker activity at other opioid receptors. ... the delta opioid receptor. In animal studies, MCOPPB produces potent anxiolytic effects, with no inhibition of memory or motor ... MCOPPB is a drug which acts as a potent and selective agonist for the nociceptin receptor, ...

*Salvinorin A

None of these compounds have shown significant (sub-micromolar) affinity at the kappa-opioid receptor, and there is no evidence ... agonist actions at kappa opioid receptors". Psychopharmacology. 179 (3): 551-8. doi:10.1007/s00213-004-2087-0. PMID 15682306. ... It acts as a kappa opioid receptor agonist and is the first known compound acting on this receptor that is not an alkaloid. ... Scheerer JR; Lawrence JF; Wang GC; Evans DA (2007). "Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor ...

*2-Methoxyethyl-18-methoxycoronaridinate

... and its effects on opioid receptors are weaker than those of 18-MC at all except the kappa opioid receptor, at which it has ... slightly higher affinity than 18-MC. 18-Methylaminocoronaridine Coronaridine Ibogaine Noribogaine Voacangine Stanley D. Glick, ... "Novel iboga alkaloid congeners block nicotinic receptors and reduce drug self-administration". European Journal of Pharmacology ...

*AP-237

... with relatively low affinity for the delta opioid receptor and the kappa opioid receptor. In accordance with these studies, ... AP-237 treated rats further indicating a mechanism of analgesia mediated via selective agonist activity at mu opioid receptors ... subsequent studies have shown AP-237 and similar acyl piperazines to be potent and selective agonists of mu opioid receptor ( ... 8-diazabicyclo3.2.1octane derivatives binding to the mu-opioid receptor". Journal of Computer-Aided Molecular Design. 7 (5): ...

*Dopamine agonist

... the psychoactivity of which is mainly due to Kappa-opioid receptor agonism; partial agonist at the D2 with an Intrinsic ... A dopamine receptor agonist is a compound that activates dopamine receptors. Dopamine receptor agonists activate signaling ... activity of 40-60%, binding affinity of Ki=5-10nM and EC50=50-90nM) Apomorphine (Apokyn - used to treat Parkinson's disease/ ... are selective for dopamine receptor D1. There are two classes of drugs that act as indirect agonists of dopamine receptors: ...

*Buprenorphine/samidorphan

Zhu J, Luo LY, Li JG, Chen C, Liu-Chen LY (1997). "Activation of the cloned human kappa opioid receptor by agonists enhances [ ... "Syntheses of novel high affinity ligands for opioid receptors". Bioorganic & Medicinal Chemistry Letters. 19 (8): 2289-2294. ... a weak partial agonist of the μ-opioid receptor (MOR), antagonist/very weak partial agonist of the κ-opioid receptor (KOR), and ... Urbano M, Guerrero M, Rosen H, Roberts E (May 2014). "Antagonists of the kappa opioid receptor". Bioorg. Med. Chem. Lett. 24 (9 ...

*Opioid antagonist

An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors ... "Discovery of the first small-molecule opioid pan antagonist with nanomolar affinity at mu, delta, kappa, and nociceptin opioid ... Many of them also bind to the κ-opioid receptor (KOR) and/or δ-opioid receptor (DOR), where they variously behave as ... The more dramatic result of naloxone versus naltrexone is suspected to be due to different opioid receptor affinity/selectivity ...

*Sigma receptor

... such drugs had no clinically relevant affinities for μ (Mu), κ (kappa), or δ (Delta) receptors. However, pharmacological ... σ-receptors were once thought to be a type of opioid receptor, because the d- stereoisomers of the benzomorphan class of opioid ... When the σ1 receptor was isolated and cloned, it was found to have no structural similarity to the opioid receptors. At this ... exact role of σ-receptors is difficult to establish as many σ-agonists also bind to other targets such as the κ-opioid receptor ...

*Dezocine

Its binding affinity varies with regards to the receptor type, as it acts as a partial agonist primarily on mu-opioid receptors ... and kappa-opioid receptors. Dezocine is a mixed agonist/antagonist of opioid receptors. It is related to other benzomorphans ... "Pharmacological profiles of opioid ligands at kappa opioid receptors". BMC Pharmacology. 6: 3. doi:10.1186/1471-2210-6-3. PMC ... Dezocine possesses affinities (Ki) of 3.7 nM, 31.9 nM, and 527 nM for the μ-, κ-, and δ-opioid receptors (MOR, KOR, and DOR), ...

*Cross-tolerance

All three of these classes each have their own receptor-mu, kappa, and delta. Opioids will bind to the receptor for the ... Most of these drugs share a high affinity for the 5-HT2A receptor subtype, known to result in their common perceptual and ... Tolerance to some effects occurs with regular use, a result of the downregulation of the stimulated opioid receptors. Cross ... These drugs block dopamine receptors and some also block serotonin receptors (such as chlorpromazine, the first antipsychotic ...

*U-69,593

"Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities". The Journal of Pharmacology ... "Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid ... Millan MJ, Członkowski A, Lipkowski A, Herz A (October 1989). "Kappa-opioid receptor-mediated antinociception in the rat. II. ... "The opioid receptor subtypes mu and kappa, but not delta, are involved in the control of the vasopressin and oxytocin release ...

*Marta Filizola

"Discovery of a novel selective kappa-opioid receptor agonist using crystal structure-based virtual screening". Journal of ... Special effort in her lab has been devoted to the subfamily of opioid receptors to discover/design novel painkillers with ... "Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS ... Provasi D, Bortolato A, Filizola M (2009). "Exploring molecular mechanisms of ligand recognition by opioid receptors with ...

*Naltriben

... evidence for differential kappa interaction with the delta 1 and delta 2 opioid receptor subtypes. Life Sciences. 1994;55(4): ... which makes it useful for distinguishing the subtype selectivity of drugs acting at the δ receptors. It also acts as a κ-opioid ... It has similar effects to the more widely used δ antagonist naltrindole, but with different binding affinity for the δ1 and δ2 ... Naltriben is a potent and selective antagonist for the delta opioid receptor, which is used in scientific research. ...

*Quadazocine

"Pharmacological profiles of opioid ligands at kappa opioid receptors". BMC Pharmacology. 6: 3. doi:10.1186/1471-2210-6-3. PMC ... but with a significant preference in affinity for the μ receptor and the κ2 subtype. As such, it has been touted as a "κ2- ... evidence of kappa opioid receptor multiplicity in the heart". Journal of Molecular and Cellular Cardiology. 31 (2): 355-62. doi ... "Multiple opioid receptor profile in vitro and activity in vivo of the potent opioid antagonist Win 44,441-3". Life Sciences. 33 ...

*LY-2459989

... and the δ-opioid receptor (Ki = 91.3 nM) (over 43-fold selectivity for the KOR over the other opioid receptors). LY-2459989 is ... It possesses high affinity for the KOR (Ki = 0.18 nM) and is highly selective for it over the μ-opioid receptor (Ki = 7.68 nM) ... "Fluorine-18-Labeled Antagonist for PET Imaging of Kappa Opioid Receptors". ACS Chem Neurosci. 8 (1): 12-16. doi:10.1021/ ... application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer". J. Med. Chem. 54 (23): ...

*Nociceptin receptor

... opioid receptors μ-OP (MOP), κ-OP (KOP), and δ-OP (DOP), it possesses little or no affinity for opioid peptides or morphine- ... receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene. ... μ-opioid and δ-opioid receptors, partial agonist at κ-opioid receptor) Etorphine MCOPPB (full agonist) MT-7716 Nociceptin ... "Orphanin FQ/nociceptin-mediated desensitization of opioid receptor-like 1 receptor and mu opioid receptors involves protein ...

*5'-Guanidinonaltrindole

"Selective κ Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters". PLoS ONE ... "Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats". The Journal of Pharmacology ... Negus, SS; Mello, NK; Linsenmayer, DC; Jones, RM; Portoghese, PS (2002). "Kappa opioid antagonist effects of the novel kappa ... a highly selective and potent kappa-opioid receptor antagonist". European Journal of Pharmacology. 396 (1): 49-52. doi:10.1016/ ...

*Etorphine

... and κ-opioid receptors. It also has relatively weak affinity for the nociceptin receptor. Etorphine has an LD50 of 30μg in ... "Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology. 6 (1): 3. doi:10.1186/1471-2210-6-3. ... "Opioid activity profiles indicate similarities between the nociceptin/orphanin FQ and opioid receptors". Eur. J. Pharmacol. 389 ... Diprenorphine (Revivon) is an opioid receptor antagonist that can be administered in proportion to the amount of etorphine used ...

*Alazocine

... δ-opioid receptors in guinea pig brain membranes) and instead is a selective and high-affinity agonist of the σ1 receptor (Ki ... "Pharmacological profiles of opioid ligands at kappa opioid receptors". BMC Pharmacol. 6: 3. doi:10.1186/1471-2210-6-3. PMC ... antagonist of the μ-opioid receptor, and to a far lesser extent agonist of the δ-opioid receptor with very low affinity for the ... The receptor was initially thought to be an opioid receptor, and then was confused with the NMDA receptor for a time, but was ...

*Lofentanil

"Pharmacological profiles of opioid ligands at Kappa opioid receptors". BMC Pharmacology. 6 (1): 3. doi:10.1186/1471-2210-6-3. ... "Study on mechanism of interaction of nociceptin and opioids binding with opioid receptor-like 1 receptor". Acta Pharmacologica ... due to their high binding affinity triggering rapid internalization of chronically activated opiate receptors. This might be ... In addition to acting on the μ-opioid receptor, lofentanil has also been found to act as a full agonist of the κ-opioid ...

*Dynorphin

... the peptides do have some affinity for the μ-opioid receptor (MOR), δ-opioid receptor (DOR), and the N-methyl-D-aspartic acid ( ... Xin L, Geller EB, Adler MW (April 1997). "Body temperature and analgesic effects of selective mu and kappa opioid receptor ... NMDA)-type glutamate receptor. Different dynorphins show different receptor selectivities and potencies at receptors. Big ... Other studies have identified a role for dynorphin and kappa opioid receptor stimulation in neuropathic pain. This same group ...

*Noribogaine

... noribogaine acts as a weak NMDA receptor antagonist and binds to opioid receptors. It has greater affinity for each of the ... "Kappa Opioid Receptor-Induced Aversion Requires p38 MAPK Activation in VTA Dopamine Neurons". J. Neurosci. 35 (37): 12917-31. ... Recently, noribogaine has been determined to act as a biased agonist of the κ-opioid receptor (KOR). It activates the G protein ... "Noribogaine is a G-protein biased κ-opioid receptor agonist". Neuropharmacology. 99: 675-88. doi:10.1016/j.neuropharm.2015.08. ...

*Cocaine intoxication

... and kappa-opioid receptors. Emergency treatment of cocaine-associated hyperthermia consists of administering a benzodiazepine ... Kivell, Bronwyn M.; Ewald, Amy W. M.; Prisinzano, Thomas E. (2014-01-01). "Salvinorin A analogs and other κ-opioid receptor ... re-uptake transporters with equal affinity. Monoamines accumulate in the synaptic cleft resulting in enhanced and prolonged ... Narayanan, Sanju; Mesangeau, Christophe; Poupaert, Jacques H.; McCurdy, Christopher R. (2011-01-01). "Sigma receptors and ...

*Neuropeptide FF receptor

"Anoretic effects of neuropeptide FF are mediated via central mu and kappa subtypes of opioid receptors and receptor ligands". ... which exhibit a high affinity for Neuropeptide FF (NPFF) peptides. NPFF1 is broadly distributed in the central nervous system ... is involved in nociception and modulation of opioid functions These receptors participate to the modulation of opioid receptor ... "Physical association between neuropeptide FF and micro-opioid receptors as a possible molecular basis for anti-opioid activity ...
Mu and kappa opioid receptors often show antagonism in the regulation of physiological responses and behavior, including aggressive behavior. We report here our studies of the effects of acute administration of the selective mu opioid receptor antagonist CTAP (1 and 2 mg/kg, s.c.) and the selective kappa opioid receptor antagonist nor-BNI (0.5 mg/kg, s.c.) on manifestations of aggressive behavior in male C57BL/6 J mice with short (three days) and long (20 days) experience of victory in intermale confrontations. Animals with short experience of aggression were insensitive to blockade of both mu and kappa receptors. In males with long experience of aggression, administration of CTAP led to dose-dependent increases in the latent period of ...
Rationale Several lines of evidence support a role for the endogenous opioid system in mediating behaviors associated with drug dependence. Specifically, recent findings suggest that the kappa-opioid receptor (KOR) may play a role in aspects of nicotine dependence, which contribute to relapse and continued tobacco smoking. Objective The objective of this study is to determine the involvement of the KOR in the initial behavioral responses of nicotine, nicotine reward, and nicotine withdrawal using the highly selective KOR antagonist JDTic.
TY - JOUR. T1 - Binding of norbinaltorphimine (norBNI) congeners to wild-type and mutant mu and kappa opioid receptors. T2 - Molecular recognition loci for the pharmacophore and address components of kappa antagonists. AU - Larson, Dennis L.. AU - Jones, Robert M.. AU - Hjorth, Siv A.. AU - Schwartz, Thue W.. AU - Portoghese, Philip S.. PY - 2000/8/20. Y1 - 2000/8/20. N2 - Molecular modifications of both the kappa opioid antagonist norbinaltorphimine (norBNI, 1) and the kappa receptor have provided evidence that the selectivity of this ligand is conferred through ionic interaction if its N17 protonated amine group (an address) with a nonconserved acidic residue (Glu297) on the kappa receptor. In the present study, we have ...
TY - JOUR. T1 - Effects of μ- and δ-opioid receptors ligands on rhythm and contractility disorders of isolated rat heart in postischemic period. AU - Maslov, L. N.. AU - Lishmanov, Yu B.. PY - 1998. Y1 - 1998. N2 - Selective μ-opioid receptor agonist DAGO increased tolerance of isolated perfused rat heart to total ischemia (45 min) and reperfusion (60 min). Intravenous administration of DAGO (0,1 mg/kg) before of the heart isolation or direct pertusion by a solution containing DAGO (1 mg/l) prior of ischemia induction prevented reperfusion arrhythmias and subpression of cardiac contractility but had no effect on magnitude of contracture. Selective δ-opioid receptor agonist DSLET did not affect arrhythmias and cardiac contractility during postischemic period.. AB - Selective μ-opioid receptor agonist DAGO ...
0144] Although not wishing to be bound by any theory, it is believed that peripherally selective kappa opioid receptor agonist administered to subjects stimulates release of the anterior pituitary hormone prolactin. The compound is typically administered in an amount sufficient to stimulate secretion of prolactin, or stabilize or prevent or inhibit reductions or decreases in prolactin, without causing a severe side effect, such as CNS side effects or diuresis. A useful dose range of a peripherally selective kappa opioid receptor agonist can be determined by one of skill in the art through routine testing. One skilled in the art recognizes that a dose depends, in part, upon physical characteristics of the patient to be treated, e.g., body weight, as well as the route of administration, e.g., intravenous injection or transdermal delivery, and ...
U-50,488 (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide) displays analgesic actions in a variety (thermal, pressure and irritant) of assays in mice and rats. Naloxone and MR-2266 block this analgesic effect; thus it is mediated by opioid receptors. However, when compared to morphine analgesia, the naloxone and MR-2266 pA2 values for U-50,488 analgesia were much lower and higher, respectively. Likewise, although tolerance occurs to both morphine and U-50,488 analgesia, there was no cross-tolerance between these drugs, and U-50,488 does not cause morphine-type physical dependence. These observations suggest that different opioid receptors mediate the analgesic effects of morphine and U-50,488. The effects of U-50,488 appear to be mediated by the so-called kappa opioid receptor. In contrast to ...
Objective: Intracerebroventricular administration of orphanin FQ/nociceptin (OFQ/N), the endogenous agonist ligand of the opioid receptor-like (ORL-1) receptor, decreases extracellular levels of dopamine and suppresses motor activity. The presence of the ORL-1 receptor on mesoaccumbal and nigrostriatal dopaminergic neurons raises the possibility that an action along these
Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor (KOPR) agonist with a short duration of action in vivo. Pharmacological properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized. MOM-Sal B bound to KOPR with high selectivity and displayed approxima …
In pursuit of neurological therapies, the opioid system, specifically delta opioid receptors and delta opioid peptides, demonstrates promising therapeutic potential for stroke, Parkinsons disease, and other degenerative neurological conditions. Recent studies offer strong evidence in support of the therapeutic use of delta opioid receptors, and provide insights into the underlying mechanisms of action. Delta opioid receptors have been shown to confer protective effects by mediating ionic homeostasis and activating endogenous neuroprotective pathways. Additionally, delta opioid agonists such as (D-Ala 2, D-Leu 5) enkephalin (DADLE) have been shown to decrease apoptosis and promote neuronal survival. In its entirety, the delta ...
Learn about the peripherally acting Kappa Opioid Receptor Agonists that Cara Therapeutics is developing for better pruritus and pain management in patients.
Although oxycodone has been generally considered to act as a typical μ-opioid agonist in humans, preclinical studies indicate that the antinociceptive effects of oxycodone are mediated by a combination of μ-opioid and κ-opioid receptors.11,50,51,52 Consistent with this view, morphine-tolerant rats continue to exhibit analgesia with oxycodone, whereas oxycodone-tolerant rats fail to display analgesia with morphine.53 Recently, it has also been shown that oxycodone and morphine have distinctly different pharmacological profiles in rat models of neuropathic pain.54 Nevertheless, it is difficult to attribute these findings to κ-opioid receptor binding activity of oxycodone (receptor affinity greater than 1000 nm) or its metabolites (Staahl et al. 55). In human subjects, the only two metabolites with significant ...
BioAssay record AID 600430 submitted by ChEMBL: Antagonist activity at nociceptin receptor in Albino guinea pig ileum assessed as inhibition of electrically evoked twitches.
The antinociceptive effect of intrathecally (i.t.) administered protease inhibitors was tested against capsaicin (800 ng) injected into the dorsal surface of a hindpaw. Both p-hydroxymercuribenzoate (2-8 nmol), a cysteine protease inhibitor, and phosphoramidon (1-4 nmol), an endopeptidase 24.11 inhibitor in the presence of bestatin (0.25 nmol) an aminopeptidase inhibitor, administered i.t. 60 min prior to the injection of capsaicin produced a dose-dependent reduction of the capsaicin-induced paw licking and biting response. p-Hydroxymercuribenzoate (4 nmol)-induced antinociception was significantly antagonized by nor-binaltorphimine, a selective kappa-opioid receptor antagonist, but not by naltrindole, a selective delta-opioid receptor antagonist. On the other hand, phosphoramidon (4 nmol) /bestatin-induced antinociception was significantly antagonized by naltrindole, but ...
TY - JOUR. T1 - Dependence on nuclear localization signals of the opioid growth factor receptor in the regulation of cell proliferation. AU - Cheng, Fan. AU - McLaughlin, Patricia. AU - Verderame, Michael. AU - Zagon, Ian. PY - 2009/5/1. Y1 - 2009/5/1. N2 - The opioid growth factor receptor (OGFr) mediates the inhibitory action of OGF on cell replication of normal and neoplastic cells. The spatiotemporal course of OGFr nucleocytoplasmic trafficking was determined with a probe of full-length OGFr fused to enhanced green fluorescent protein (eGFP). Translation of OGFr required 8.5 hours, and transit into the nucleus required 8 hours; OGFr remained in the nucleus for 8 days. OGFr was initially expressed on the outer nuclear envelope, transited to the paranuclear cytoplasm, and into the nucleus. Transport through the nuclear pore was elucidated by mutation of the nuclear localization signal (NLS) sequences in ...
mu Opioid Receptors: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Objective: To determine whether nicotine, at the dose delivered through a cigarette (1-2 mg), will increase the release of endogenous opioids, measured by the displacement of the mu-opioid PET receptor radioligand [(11)C]carfentanil and to determine whether smokers have adaptations in the opioid system compared with nonsmokers.. Study Population: 20 current, daily smoikers and 20 never-smokers who have smoked between 1 and 20 cigarettes in their lifetime.. Design: Double-blind, placebo-controlled, parallel groups design.. Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism; and 4) correlation ...
Objective: To determine whether nicotine, at the dose delivered through a cigarette (1-2 mg), will increase the release of endogenous opioids, measured by the displacement of the mu-opioid PET receptor radioligand [(11)C]carfentanil and to determine whether smokers have adaptations in the opioid system compared with nonsmokers.. Study Population: 20 current, daily smoikers and 20 never-smokers who have smoked between 1 and 20 cigarettes in their lifetime.. Design: Double-blind, placebo-controlled, parallel groups design.. Outcome Measures: 1) displacement [(11)C]carfentanil binding, secondary to the release of endorphins by nicotine; 2) upregulation of [(11)C]carfentanil specific binding in smokers compared with nonsmokers; 3) [(11)C]carfentanil specific binding as a function of the mu-opioid receptor A118G polymorphism; and 4) correlation ...
RATIONALE. Salvinorin A is the active component of the hallucinogenic plant Salvia divinorum. The potential mode of action of this hallucinogen was unknown until recently. A recent in vitro study detected high affinity and efficacy of salvinorin A at kappa-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy kappa-agonist (U69,593) in rhesus monkeys.. METHODS. Monkeys were previously trained to discriminate U69,593 (0.0056 or 0.013 mg/kg; SC) from vehicle in a food-reinforced FR20 (fixed ratio 20) operant conditioning procedure ( n=3). The ability of salvinorin A to cause generalization (>/=90% U69,593-appropriate responding) was examined in time course and cumulative dose-effect curve studies.. RESULTS. All subjects dose-dependently emitted full U69,593-appropriate responding after salvinorin ...
Morphiceptin is a tetrapeptide (Tyr-Pro-Phe-Pro-NH2) that is a selective μ-opioid receptor agonist. It is derived from β-casomorphin and has over 1,000 times selectivity for μ- over δ-opioid receptors. When injected intracerebroventricularly (into the ventricular system of the brain), morphiceptin had an analgesic ED50 of 1.7 nmol per animal. The analgesic effects of morphiceptin were reversed by naloxone, meaning that the analgesic effect is mediated by the μ-opioid receptor. Morphiceptin is the (1S,2S,3S,4S)-form whereas deproceptin is the (1S,2S,3S,4R)-form [84799-23-5]. Casokefamide "Morphiceptin". Morphiceptin. ChemBase. Retrieved 1 August 2011. Chang, K (3 May 1982). "Analgesic activity of intracerebroventricular administration of morphiceptin and β-casomorphins: Correlation with the morphine (μ) receptor binding ...
Nociceptin orphanin FQ (N/OFQ) is the 17 amino acid endogenous ligand for the Gi-coupled N/OFQ-receptor (NOP). In vivo administration produces a wide range of physiological responses including; analgesia, hyperalgesia and anti-opioid actions.;In a series of in vitro assays including [leucyl -3H]N/OFQ binding, GTPgamma[35S] binding and inhibition of cAMP formation the following linked studies were performed; (1)N/OFQ structure-activity relationships (SAR) in cells (CHO) stably expressing human NOP (2)evaluation of receptor density on efficacy using the ecdysone inducible expression system and native tissues, (3)an investigation of NOP/G-protein coupling efficiency.;SAR studies can be summarized as combining arginine14, lysine15 repeat in N/OFQ (increase affinity/potency) with C-terminal [F/G]N/OFQ(1--13)NH2([F/G]) and [Nphe1]N/OFQ(1--13)NH 2([Nphe1]) modifications (reduce/eliminate efficacy). Arg14/Lys15 increased the ...
Kappa-opioid receptor agonists may have pharmacotherapeutic potential in the management of psychostimulant abuse, due to their ability to modulate dopamine receptor systems involved in drug reinforcement. kappa-Opioid receptor agonists also modulate dopamine receptor function in the hypothalamic tub …
Earlier studies from this laboratory had indicated that there is a selective increase in the density of brain kappa opioid receptors labeled with [3H]ethylketocyclazocine in spontaneously hypertensive (SHR) rats in comparison to normotensive Wistar-Kyoto rats. The binding of a mu-ligand, [3H]naltrexone, and a delta-ligand, [3H]Tyr-D-Ser-Gly-Phe-Leu-Thr, to brain membranes of hypertensive and normotensive rats did not differ. The present studies were undertaken to determine further the role of kappa opioid receptors in hypertension. The binding of [3H]ethylketocyclazocine to brain membranes of hypertensive rats was much greater than those of normotensive rats. The density of kappa receptors was significantly higher in hypothalamic membranes of hypertensive rats as compared to normotensive ...
The μ-opioid receptors (MOR) are a class of opioid receptors with a high affinity for enkephalins and beta-endorphin, but a low affinity for dynorphins. They are also referred to as μ-opioid peptide (MOP) receptors. The prototypical μ-opioid receptor agonist is morphine, the primary psychoactive alkaloid in opium. It is an inhibitory G-protein coupled receptor that activates the Gi alpha subunit, inhibiting adenylate cyclase activity, lowering cAMP levels. Three variants of the μ-opioid receptor are well characterized, though RT-PCR has identified up to 10 total splice variants in humans. They can exist either presynaptically or postsynaptically depending upon cell types. The ...
TY - JOUR. T1 - Prospects of Using of κ-Opioid Receptor Agonists U-50,488 and ICI 199,441 for Improving Heart Resistance to Ischemia/Reperfusion. AU - Tsibulnikov, S. Yu. AU - Maslov, L. N.. AU - Mukhomedzyanov, A. V.. AU - Krylatov, A. V.. AU - Tsibulnikova, M. R.. AU - Lishmanov, Yu B.. PY - 2015/10/1. Y1 - 2015/10/1. N2 - We studied the ability of the agonist of κ1-opioid receptors U-50,488 in doses of 0.1 and 1 mg/kg to simulate ischemic pre- and postconditioning of the heart and κ-opioid receptors ICI 199,441 in a dose of 0.1 mg/kg to simulate the antiarrhythmic effect of heart preconditioning. The duration of ischemia was 10 or 45 min and the duration of reperfusion was 10 min or 2 h. Administration of 1 mg/kg U-50,488 both before ischemia and 5 min before reperfusion produced a pronounced antiarrhythmic effect. U-50,488 injected 5 min before ...
Preferred Name: Opioid Growth Factor Definition: An endogenous pentapeptide with potential antineoplastic and antiangiogenic activities. Opioid growth factor (OGF) binds to and activates the OGF receptor, present on some tumor cells and vascular cells, thereby inhibiting tumor cell proliferation and angiogenesis. (NCI05) NCI-GLOSS Definition: A substance that relieves pain and is being studied in the treatment of some types of cancer. Opioid growth factors bind to cells in the body, including tumor cells, which have opioid growth factor receptors on the surface. This may help stop the growth of the tumor cells. It may also prevent the growth of blood vessels that tumors need to grow. An opioid growth factor is a type of biological response modifier and a type of antiangiogenesis agent. Label: ...
This invention relates to a method of selectively enhancing the analgesic potency of morphine and other clinically used bimodally-acting opioid agonists and simultaneously attenuating development of physical dependence, tolerance and other undesirable side-effects caused by the chronic administration of said bimodally-acting opioid agonists comprising the co-administration of a bimodally-acting opioid agonist which activates inhibitory opioid receptor-mediated functions of neurons in the nociceptive (pain) pathways of the nervous system and an opioid receptor antagonist which selectively inactivates excitatory opioid receptor-mediated side-effects caused by said bimodally-acting opioid agonists. This invention further ...
The varied behavioral effects of kappa opioid receptors (KOR) are mediated through different signaling cascades. KOR activation of G protein-dependent signaling results in analgesia, whereas the dysphoric effects are mediated by a different pathway involving G protein-coupled receptor kinase (GRK) and arrestin. Therefore, a partial KOR agonist that does not efficiently activate arrestin-dependent signaling may produce analgesia without dysphoria. No selective KOR partial agonists are currently available, and preclinical assessment is complicated by sequence differences between rodent (r) and human (h) KOR. KOR antagonists are also of therapeutic interest for their potential anxiolytic and antidepressant effects, but many KOR antagonists have long durations of action resulting from selective activation of cJun kinase (JNK). In this thesis, I compared the signaling events initiated by agonist stimulation of ...
TY - JOUR. T1 - Side chain methyl substitution in the δ-opioid receptor antagonist TIPP has an important effect on the activity profile. AU - Tourwé, Dirk. AU - Mannekens, Els. AU - Diem, Trang Nguyen Thi. AU - Verheyden, Patricia. AU - Jaspers, Hendrika. AU - Töth, Géza. AU - Péter, A.. AU - Kertész, Istvân. AU - Török, Gabriella. AU - Chung, Nga N.. AU - Schiller, Peter W.. PY - 1998/12/17. Y1 - 1998/12/17. N2 - The δ-opioid antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP-OH) or its C- terminal amide analogue was systematically modified topologically by substitution of each amino acid residue by all stereoisomers of the corresponding β-methyl amino acid. The potency and selectivity (δ-vs μ- and κ-opioid receptor) were evaluated by radioreceptor binding assays. Agonist or antagonist potency were assayed in the mouse vas deferens and in the guinea pig ileum. In the ...
TY - JOUR. T1 - Antinociceptive effects of Salvia divinorum and bioactive salvinorins in experimental pain models in mice. AU - Tlacomulco-Flores, Lorenzo Leonel. AU - Déciga-Campos, Myrna. AU - González-Trujano, María Eva. AU - Carballo-Villalobos, Azucena Ibeth. AU - Pellicer, Francisco. PY - 2020/2/10. Y1 - 2020/2/10. N2 - Ethnopharmacological relevance: Salvia divinorum Epling & Játiva is a Mexican plant used not only in rituals but also in traditional medicine for pain relief. One of the most known bioactive compounds is salvinorin A, which acts centrally in kappa-type opioid receptors. Aim of the study: Despite its traditional use as a medicinal plant, there is not enough scientific investigation to reinforce its potential as analgesic. In this study, Salvia divinorum antinociceptive activity was evaluated in experimental models of nociceptive pain; the writhing test and formalin-induced licking behavior in mice. ...
Previous pharmacological studies have indicated the possible existence of functional interactions between μ-, δ- and κ-opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of δ- and κ-opioid receptors in mice lacking the μ-opioid receptor (MOR). Measurements of agonist-induced [35S]GTPγS binding and adenylyl cyclase inhibition showed that functional coupling of δ- and κ-receptors to G-proteins is preserved in the brain of mutant mice. In the mouse vas deferens bioassay, deltorphin II and cyclic[d-penicillamine2,d-penicillamine5] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR −/− mice. δ-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. ...
Psychopharmacology (Berl). 2013 Jul;228(2):207-15. doi: 10.1007/s00213-013-3023-y. Epub 2013 Feb 22. Research Support, Non-U.S. Govt
Hi andrew, thanks for ur suggestions on opioid receptors actually we r doing immuno on zebrafinch bird brain sections 40 micron thick we have got opioid receptors from sigma , but after repeat trials we r not able to localise opioid receptors in brain sections we have tried with mu.delta and kappa but non is working till now , we have done western blot and were able to get two bands nearly 45-49 kd can u tell why there r two bands there............ can u do me a favour by suggesting some protocol in detail, i will be thanfull to u for that, if u can pls mail by earliest at .................................................. [email protected] ...
(trans)-Isomer 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide: A non-peptide, kappa-opioid receptor agonist which has also been found to stimulate the release of adrenocorticotropin (ADRENOCORTICOTROPIC HORMONE) via the release of hypothalamic arginine vasopressin (ARGININE VASOPRESSIN) and CORTICOTROPIN-RELEASING HORMONE. (From J Pharmacol Exp Ther 1997;280(1):416-21)
BioAssay record AID 149839 submitted by ChEMBL: In vitro inhibition for opioid binding site in guinea pig brain membrane using [3H]U-69593 as radioligand.
Dynorphin B is an agonist of nuclear opioid receptors coupling nuclear protein Kinase C activation to the transcription of cardiogenic genes in GTR1 embryonic stem cells. Dynorphin B is a form of dynorphin.Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and a/b-neo-endorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of "big dynorphin."This 32-amino acid molecule consists of both dynorphin A and dynorphin B.Dynorphin A, dynorphin B, and big dynorphin all contain a high proportion of basic amino acid residues, in particular lysine and arginine (29.4%, 23.1%, and ...
g of salvinorin A induces profound hallucinations.10 Salvinorin A is the first diterpene to be identified as a hallucinogen in humans and is one of the most potent naturally occurring compounds thus far isolated.11 We have discussed the effects of S. divinorum and salvinorin A in animals and humans and warned of their potential to become drugs of abuse.5 During our research on S. divinorum, salvinorin A was first isolated from a single pharmacologically active TLC band using a solvent system of 100/10/1 CHCl3/MeOH/H2O. Differences in potency between the purified diterpene and the original TLC fraction led us to surmise that the latter contained other strongly bioactive compounds that co-chromatographed with salvinorin A during the chromatographic separation. Upon changing the solvent system to 1/1 hexanes/EtOAc, the minor component became separated from salvinorin A. Even though it is estimated that salvinorin C comprises only about 10% of the pharmacologically active TLC fraction, the rest ...
The clerodane diterpenoid salvinorin A (1), the main active component of the psychotropic herb Salvia divinorum, has been reported to be a potent agonist at the kappa-opioid receptor. Computer modeling suggested that splendidin (2) from S. splendens, as well as related compounds, might possess similar activities. In the present study, this hypothesis was tested by determination of the binding properties of a series of structural congeners, compounds 2-8, at the mu-, delta-, and kappa-opioid receptors. However, none of these compounds showed significant binding to any of the opioid-receptor subtypes, thus disproving the above hypothesis. The novel compounds 7 and 8 were obtained semi-synthetically by selective modification of salvifarin (5), isolated from Salvia farinacea, upon epoxide-ring ...
Investigations on gastric mucosal protective mechanisms are focused mainly on the local mucosal processes. Much less is known about how the central nervous system may influence the gastric mucosal defense. However, gastric mucosal protection induced by a central mechanism was described recently (Tache et al., 1994; Gyires, 1997;Guidobono et al., 1998; Kaneko et al., 1998; Yang et al., 1999). In our present study, the role of central opioid receptors was analyzed by means of selective δ- and μ-opioid receptor agonists. It was found that both the selective δ- and μ-opioid receptor agonists injected either i.c.v. or i.c. exerted protective effect against acidified ethanol-induced lesions; the rank order of potency was β-endorphin , DAGO , DADLE , deltorphin II , DPDPE following i.c.v. injection and deltorphin II , β endorphin , DPDPE , DAGO , DADLE following ...
κ opioid receptor activation by traditional arylacetamide agonists and the novel neoclerodane diterpene κ opioid receptor agonist Salvinorin A (Sal A) results in attenuation of cocaine-seeking behavior in pre-clinical models of addiction. However, adverse effects such as sedation, depression and aversion limit their clinical utility. The Sal A analogue, 2-methoxymethyl salvinorin B (MOM Sal B) is a longer acting Sal A analogue with high affinity for κ opioid receptors. In this study, we tested MOM Sal B for its ability to modulate cocaine-seeking behavior in rats. MOM Sal B (0.3 mg/kg) successfully attenuated cocaine-seeking but also attenuated sucrose reinforcement. No change in activity was observed in either cocaine-induced hyperactivity or spontaneous open field activity tests but increased immobility and decreased swimming times in the ...
Agonists targeting MOR are effective analgesics, but their clinical use is hindered by side effects, including tolerance and addiction. KOR agonists also produce analgesia, but clinical use of these compounds has remained minimal due to aversive properties in humans. The µ-opioid receptor (MOR) agonists, morphine and fentanyl, both activate c-Jun N-terminal kinase (JNK), which is required for spinally-mediated morphine acute analgesic tolerance, whereas acute analgesic tolerance to fentanyl is blocked by G protein-coupled receptor kinase 3 (GRK3) gene deletion. Similarly, the κ-opioid receptor (KOR) collateral antagonist, norBNI, stimulates phosphorylation of JNK, and JNK1 is specifically required for norBNIs long duration of antagonism. The durations of action of a broad range of KOR antagonists, including norBNI, positively correlate with the ability of the antagonist to activate JNK1 ...
TY - JOUR. T1 - A novel acetylated analogue of dynorphin A-(1-11) amide as a κ-opioid receptor antagonist [1]. AU - Wan, Qiang. AU - Murray, Thomas F.. AU - Aldrich, Jane V.. PY - 1999/8/12. Y1 - 1999/8/12. UR - http://www.scopus.com/inward/record.url?scp=0033549868&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0033549868&partnerID=8YFLogxK. U2 - 10.1021/jm9901071. DO - 10.1021/jm9901071. M3 - Letter. C2 - 10447942. AN - SCOPUS:0033549868. VL - 42. SP - 3011. EP - 3013. JO - Journal of Medicinal Chemistry. JF - Journal of Medicinal Chemistry. SN - 0022-2623. IS - 16. ER - ...
Traditionally, a 1:1 ratio in analgesic potency between intravenous morphine and oxycodone has been presumed (1-2), but one study demonstrated a 3:2 ratio between those drugs (3). During the last years, several studies indicate that oxycodone has the potential of mediating pain relief through the kappa-opioid receptor (4-6), and not only on the my-opioid receptor like most other opioids used in the clinic. Kappa-opioid receptors are widely distributed in visceral organs, and this may explain why Kalso (3) found less need for oxycodone compared to morphine in patients undergoing abdominal surgery.. The aim of this study is to investigate whether patients with visceral postoperative pain need less oxycodone compared to morphine, and whether patients receiving ...
Really great post! As someone who has spent their post-doc actively investigating the Kappa opioid receptor I find the ban in 13 states on Salvinorin A to be another example of political leaders who know nothing about science making senseless policy. Anything that is fun, introspective, or novel must therefore be dangerous. A "Public Health Concern" is just plain silly, if you ask me. How many examples of accident or death have resulted from Sal A use? How many from alcohol? How many from cigarettes? The Pacific NW has yet to ban "Sal A", and Im doubting it is the first priority for many of the legislators up here considering we have bigger and more important things to deal with…. A few things that are worth mentioning. 1) Kappa opioid receptor (KOR) agonists are dysphoric. (See Land et al, 2008; Pfeiffer et al., 1986) Ive listened to some ...
In previous studies, we have provided evidence that prodynorphin gene expression and dynorphin B expression orchestrate cardiac differentiation in P19 embryonal carcinoma cells.7 The present investigation has revealed that dynorphin B-like material is detectable in undifferentiated GTR1 ES cells and that a substantial increase in dynorphin B-related immunostaining occurs in ES-derived cardiomyocytes. The possibility that the process of cardiogenesis may require the intracellular action of dynorphin peptides is supported by the observation that κ opioid binding sites are expressed in a highly purified preparation of ES cell nuclei. Such a hypothesis is further inferred from the finding that a direct exposure to dynorphin B of nuclei isolated from undifferentiated cells results in a remarkable activation of the transcription rate of GATA-4, Nkx-2.5, and prodynorphin genes. Within this context, the observed increase in the Bmax value for the selective κ ...
Salvia Divinorum Learning Objectives Terminal Learning Objective: The unit commander will become familiar with Salvia Divinorum and be able to determine the impact it may have on the unit personnel and/or readiness Enabling Learning Objectives: Slideshow 30029 by Ava
The Index page for the reference article: Wu LT, Woody GE, Yang C, Li JH, Blazer DG Recent national trends in Salvia divinorum use and substance-use disorders among recent and former Salvia divinorum users compared with nonusers Subst Abuse Rehab 2011 2:53-68
Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for ? opioid receptors. One approach to better understanding the mode of binding of 1 at ? receptors is to systematically alter the structure of 1 and examine the effects on opioid receptor affinity and activity.
The Salvia Divinorum plant has large green leaves and can grow to over a meter high. The plant occasional blossoms white and purple flowers and has stems that are hollow, and square.. Flourishing in the shady, damp soil, the herb is most famous for its strong, natural chemical counterpart, Salvinorin A.. Salvinorin A is activated by smoking, chewing or drinking the plant as a tea-like drink. In smoking the herb, the temperature has to reach 240 degrees Celsius in order to effectively induce the desired a psychedelic-like state. While smoking is the most assumed method for activating the Salvinorin A, chewing and drinking the plant as a tea increases the amount of Salvinorin A intake.. Chewing the leaves means the leaf has to remain in the mouth as long as possible. The actual ingestion of the leaves voids the drug reaction due to the gastrointestinal power to neutralize the Salvinorin A, rendering ingestion presumably harmless.. Salvinorin A is currently the most potent psychoactive drug ...
TY - JOUR. T1 - Neuroprotective κ-opioid receptor agonist BRL 52537 attenuates ischemia-evoked nitric oxide production in vivo in rats. AU - Goyagi, Toru. AU - Toung, Thomas J K. AU - Kirsch, Jeffrey. AU - Traystman, Richard J.. AU - Koehler, Raymond C.. AU - Hum, Patricia D.. AU - Bhardwaj, Anish. PY - 2003/6/1. Y1 - 2003/6/1. N2 - Background and Purpose - κ-Opioid receptors (KOR) have been implicated in neuroprotection from ischemic neuronal injury. We tested the effects of a selective and specific KOR agonist, BRL 52537 hydrochloride [(±)-1-(3,4- dichlorophenyl)acetyl-2-(1-pyrrolidinyl) methylpiperidine], on infarct volume and nitric oxide production after transient focal ischemia in the rat. Methods - With the use of the intraluminal filament technique, halothane-anesthetized male Wistar rats (weight, 250 to 300 g) were subjected to 2 hours of focal cerebral ischemia confirmed by Doppler flowmetry. In a ...
The average values of chemical analytes found in the smoke of a tobacco and an S. divinorum cigarette are listed in Table I. Excluding the psychoactive constituents of the respective plants, most of the analytes were found in similar amounts in the two plants. The S. divinorum plant material used in this study demonstrated some variation even within the small sampling of the leaf material used for the smoking studies. The three samples analyzed for 2.20 ± 0.30, 3.82 ± 0.65 and 3.69 ± 0.04 mg salvinorin A per gram of plant material (n = 4 for each determination). The grand average of these determinations is 3.24 mg salvinorin A per gram of plant material or 0.324% of the dried plant material, which is near the average 0.245% salvinorin A content reported by Siebert (3). An 830 mg cigarette would then have ∼2.7 mg salvinorin A present. In the smoke, 133 μg of salvinorin A was delivered (∼5% yield) indicating significant conversion of salvinorin A to other components during combustion. Some ...
Hypoxia adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of hypoxia in which they may begin to die when oxygen supply is reduced or completely eliminated. Opioid receptor agonists have been shown to elicit several central nervous system effects, mediated via G protein-coupled receptors. The aim of this study was to study the effect of hypoxia on G protein coupled receptor gene expression using mu opioid receptor as a case study in cortical neuronal B50 cell lines in culture. The B50 cells were cultured in normoxia (21% O2; 5% CO2) and hypoxia (5% O2; 5% CO2), and were treated with opioid agonists to determine their effects on hypoxia-induced changes. Three opioid agonists {DAMGO(μ), DSLET(δ) and ICI--199,441(κ)}, were ...
Salvinorin A je glavni aktivni psihotropni molekul u meksičkoj biljci Salvia divinorum[5], koja ima dugu istoriju upotrebe kao enteogen među autohtonim mazatečkim šamanima. Salvinorin A je halucinogeno jedinjenje sa psihodeličnim/disocijativnim efektima.. On je strukturno različit od drugih prirodnih halucinogena (kao što su DMT, psilocibin, i meskalin) zato što sadrži atome azota, i stoga nije alkaloid.. Salvinorin A može da proizvede psihoaktivne doživljaje kod ljudi sa tipičnim trajanjem od nekoliko minuta od jednog sata, u zavisnosti od metoda unosa.[6]. Salvinorin A je nađen sa nekoliko drugih strukturno-srodnih salvinorina. Salvinorin je trans-neoklerodan diterpenoid. On deluje kao agonist kapa opioidnog receptora. Salvinorin A je bio prvo jedinjenje za koje se znalo da deluje na ovaj receptor koje nije alkaloid. Njega je izolovao Alfredo Otega u Meksiku 1982, a njegov farmakološki mehanizam je ispitan u laboratoriji Brajana L. Rota.. ...
Salvinorin A je glavni aktivni psihotropni molekul u meksičkoj biljci Salvia divinorum[1], koja ima dugu istoriju upotrebe kao enteogen među autohtonim mazatečkim šamanima. Salvinorin A je halucinogeno jedinjenje sa psihodeličnim/disocijativnim efektima.. On je strukturno različit od drugih prirodnih halucinogena (kao što su DMT, psilocibin, i meskalin) zato što ne sadrži atome azota, i stoga nije alkaloid.. Salvinorin A može da proizvede psihoaktivne doživljaje kod ljudi sa tipičnim trajanjem od nekoliko minuta do jednog sata, u zavisnosti od metoda unosa.[2]. Salvinorin A je nađen sa nekoliko drugih strukturno-srodnih salvinorina. Salvinorin je trans-neoklerodan diterpenoid. On deluje kao agonist kapa opioidnog receptora. Salvinorin A je bio prvo jedinjenje za koje se znalo da deluje na ovaj receptor koje nije alkaloid. Njega je izolovao Alfredo Otega u Meksiku 1982, a njegov farmakološki mehanizam je ispitan u laboratoriji Brajana L. ...
IBNtxA, a morphine derivative, is 10-fold more potent and has a better safety profile than morphine. The animal studies indicate that the IBNtxA analgesia appears to be mediated by activation of the truncated spice variants (6TM) of Mu Opioid receptor (MOR-1) where transmembrane helix 1 (TM1) is removed. Int
A combination of drugs including a kappa opioid receptor agonist and a dopamine receptor blocker or dopamine receptor agonist provides a synergistic effect in inducing hypothermia and/or poikilothermia in humans and animals. Hypothermia as much as 10 C. at an ambient temperature of 20 C. is possible, with complete recovery and few, if any, side effects.
The principal active component of S. divinorum is salvinorin A. Although a number of other compounds have been isolated from the plant, including salvinorins B-I, their biological activity remains to be elucidated. The concentration of salvinorin A in leaves collected from separate plants, even genetically identical ones, can vary considerably. In vitro and in vivo studies have demonstrated that salvinorin A is a selective and potent agonist of k-opioid receptors (KOR), and has no structural resemblance to any known hallucinogens, such as LSD. Of particular importance is the fact that salvinorin A has no affinity for other known receptors for psychoactive compounds, such other opioid receptors, cannabinoid receptors, cholinergic receptors, glutamate receptors, and serotonin (5-HT) receptors, including ...
At the molecular level, drugs like salvinorin A (the active ingredient of the hallucinogenic plant Salvia divinorum) work by activating specific proteins, known as receptors, in the brain and body.. Salvinorin A, the most potent naturally occurring hallucinogen, is unusual in that it interacts with only one receptor in the human brain - the kappa opioid receptor (KOR). Scientists know of four distinct types of opioid receptors, but until now the structure of the salvia receptor, and the details about how salvinorin A and other drugs interact with it, was a mystery.. In a research paper published March 21 in the journal Nature, scientists from the University of North Carolina at Chapel Hill, Scripps Research Foundation and two other institutions revealed the first-ever glimpse of the complete structure of the KOR. The finding ...
The µ-opioid receptor is the primary target structure of most opioid analgesics and thus responsible for the predominant part of their wanted and unwanted effects. Carriers of the frequent genetic µ-opioid receptor variant N40D (allelic frequency 8.2 - 17 %), coded by the single nucleotide polymorphism A|G at position 118 of the µ-opioid receptor coding gene OPRM1 (OPRM1 118A|G SNP), suffer from a decreased opioid potency and from a higher need of opioid analgesics to reach adequate analgesia. The aim of the present work was to identify the mechanism by which the OPRM1 118A|G SNP decreases the opioid potency and to quantify its effects on the analgesic potency and therapeutic range of opioid ...
Metazocine is an opioid analgesic related to pentazocine. While metazocine has significant analgesic effects, mediated through a mixed agonist-antagonist action at the mu opioid receptor, its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors (where it is a high-efficacy agonist) and/or sigma receptors. Metazocine is in Schedule II of the Controlled Substances Act 1970 of the United States as a Narcotic with ACSCN 9240 with a 19 gram aggregate manufacturing quota as of 2014. The free base conversion ratio for salts includes 0.81 for the hydrochloride and 0.74 for the hydrobromide. It is listed under the Single Convention for the Control of Narcotic Substances 1961 and is controlled in most countries in the same fashion as is morphine. The ...
This topic has 4 study abstracts on Salvia divinorum indicating that it may have therapeutic value in the treatment of Diarrhea, Anxiety Disorders, and Depression: Unipolar
An Experience with Salvia divinorum (5x & 15x extracts) & Nitrous Oxide (Whippets). This Is Where Consciousness Comes From by Zap Brannegan
DEPARTMENT OF HEALTH. CONTROLLED DRUGS AND SUBSTANCES ACT. Notice to interested parties - Proposal regarding the addition of Salvia divinorum and salvinorin A to Schedule III to the Controlled Drugs and Substances Act. This notice provides interested stakeholders with the opportunity to provide comments on Health Canadas proposal to add the plant Salvia divinorum (S. divinorum) and its main active ingredient salvinorin A to Schedule III to the Controlled Drugs and Substances Act (CDSA). Stakeholders may also identify themselves for inclusion in any future consultation.. The plant S. divinorum is a species of sage belonging to the mint family. Its leaves are generally chewed or smoked to obtain psychotropic effects. While uncertainty remains surrounding the health risks of S. divinorum, known effects are reported to be short-acting in nature and include hallucinations, dysphoria, out-of-body experiences, unconsciousness and short-term memory loss. The effects, which vary from person to person, ...
konfirmi) Tifluadom [1] estas benzodiazepin derivaĵo kun nekutima agadprofilo. Male al la plej multaj benzodiazepinoj, tifluadom havas neniun agadon ĉe la GABAA receptoro, sed anstataŭe estas selektema agonisto por la κ-opioid receptoro. [2] En konformo, ĝi havas potencan kontraŭdolorilon [3] kaj urinigaj [4] efikoj en bestoj, kaj ankaŭ havas sedativajn efikojn kaj stimulas apetiton.. Dum tifluadom havas plurajn efikojn kiuj eble havos eblajn uzojn en medicino kiel ekzemple analgezio kaj apetitstimulo, κ-opioid agonistoj tendencas produkti nedezirindajn efikojn en homoj kiel ekzemple disforio kaj halucinoj, kaj tiel tiuj medikamentoj tendencas nur esti uzitaj en scienca esplorado. Disforaj efikoj estas similaj al tiuj viditaj kiam uzado de aliaj κ-opioid receptoragonistoj kiel pentazocino kaj salvinorin A.. ...
Our previous study showed that electroacupuncture (EA) significantly attenuated inflammatory hyperalgesia. It has also been reported that EA analgesia in uninjured animals is mediated by μ and δ opioid receptors at 2-15 Hz and by κ opioid receptor at 100 Hz. Because persistent pain changes neural response to external stimulation, we hypothesized that (1) the mechanisms of EA anti-hyperalgesia may be different under conditions of persistent pain and that (2) combining EA with a sub-effective dose of morphine could enhance EA anti-hyperalgesia. Hyperalgesia, decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, was induced by subcutaneously injecting complete Freunds adjuvant (CFA) into the hind paws of rats. Selective antagonists against μ (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-ThrNH2, CTOP), δ (naltrinodole, NTI) and κ (nor-binaltorphimine, BNI) opioid ...
The principal findings of these experiments provide new insight into the mechanisms underlying the dysphoric response to stress. κ-Opioid receptor activation after forced swim, inescapable footshock or κ-agonist administration each produced aversion by dynorphin/KOR-dependent mechanisms. CRF receptor-selective agonists and antagonists showed that the aversion resulted from CRF2-R activation. Imaging of the brain regions mediating the response using the phospho-selective KORp antibody (McLaughlin et al., 2003b) showed that brain regions that may mediate this response correspond to those previously associated with negative affective state (Carrasco and Van de Kar, 2003). The resulting evidence strongly implicates the endogenous dynorphin system as a key mediator of the dysphoric response to stress.. In this study, we used conditioned place aversion as an objective measure of behavior and infer a relationship between the aversion measured and ...
A class of opioid peptides including dynorphin A, dynorphin B, and smaller fragments of these peptides. Dynorphins prefer kappa-opioid receptors (RECEPTORS, OPIOID, KAPPA) and have been shown to play a role as central nervous system transmitters ...
The opioid peptide dynorphin is expressed by certain neurons in the superficial dorsal horn of the spinal cord, but little is known about the types of cell that contain dynorphin. In this study, we have used an antibody against the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were to estimate the proportion of neurons in each of laminae I-III that express dynorphin and to determine whether they are excitatory or inhibitory neurons. PPD-immunoreactive cells were concentrated in lamina I and the outer part of lamina II (IIo), where they constituted 17% and 8%, respectively, of all neurons. Around half of those in lamina I and 80% of those in lamina II were GABA-immunoreactive. We have previously identified four non-overlapping neurochemical populations of inhibitory interneurons in this region, defined by the presence of neuropeptide Y, galanin, parvalbumin and neuronal ...
Racemorphan, or morphanol, is the racemic mixture of the two stereoisomers of 17-methylmorphinan-3-ol, each with differing pharmacology and effects: Dextrorphan - an antitussive and dissociative hallucinogen (NMDA receptor antagonist) Levorphanol - an opioid analgesic Racemorphan itself is under international control per the Single Convention on Narcotic Drugs 1961 and is therefore listed as a Schedule II Narcotic controlled substance in the US Controlled Substances Act 1970; it has an ACSCN of 9733 and in 2014 it had an aggregate annual manufacturing quota of zero. The salts in use are hydrobromide (free base conversion ratio 0.741), hydrochloride (0.876), and tartrate (0.632 ...
Although the use of the mushrooms and morning glories was documented by the Spanish conquistodores and chroniclers who arrived in Mexico during the Sixteenth Century (Wasson, 1963), the literature on S. divinorum is relatively recent. Wasson originally proposed that this Salvia was the plant known to the Spanish by the Nahuatl (Aztec) name of pipiltzintzintli, but new investigations suggest that the Mexican name probably refers to Cannabis sativa I,. (Diaz, 1979).. There are a number of common names for S. divinorum and nearly all are related to the plants association with the Virgin Mary. It is known to the Mazatecs as ska Maria Pastora, the leaf or herb of Mary, the Shepherdess. The name is usually shortened to ska Maria or ska Pastora and the sage is also known by a number of Spanish names including hojas de Maria, hojas de la Pastora, hierba (yerba) Maria or la Maria. The Mazatecs believe this Salvia to be an incarnation of the Virgin Mary, and care is taken to avoid trampling on or ...
Dezocine (INN, USAN) (brand name Dalgan) is a marketed opioid analgesic of the benzomorphan group. First synthesized in 1970, it acts as a modulator of mu-, delta-, and kappa-opioid receptors. Dezocine is a mixed agonist/antagonist of opioid receptors. It is related to other benzomorphans such as pentazocine, with a similar profile of effects that include analgesia and euphoria. Unlike many other benzomorphans however, it is a silent antagonist of the κ-opioid receptor, and in accordance, does not produce side effects such as dysphoria or hallucinations at any dose. Dezocine was patented by American Home Products Corp. in 1978. Clinical trials ran from 1979-1985, before its approval by the U.S. Food and Drug Administration (FDA) in 1986. As of 2011, dezocines usage is discontinued in the ...
The pharmacological effects of opioids in opioid dependent individuals can vary as a function of the characteristics of the opioid being studied (e.g., whether it is an agonist, partial agonist, or antagonist; the dose administered; and the route of administration). Another important set of factors influencing the effects produced by opioids is the characteristics of the organism to which the opioid is being administered. One such characteristic is the level of physical dependence in individuals.. Participants in this study will be maintained on different dose levels of an opioid agonist (methadone). The participant will be challenged with a prototypic opioid agonist, antagonist, and a mixed agonist-antagonist with partial agonist features in order to determine the effects ...
At present, divergent views exist concerning the extent to which either opioid receptor desensitization or adenylate cyclase superactivation contribute to the development of tolerance to morphine. The receptor activity versus endocytosis (RAVE) model proposes that morphine may induce adenylate cyclase superactivation to a greater extent than other opioids, which in turn exacerbates the development of tolerance (Whistler et al, 1999; Finn and Whistler, 2001). In contrast, studies using mice lacking β‐arrestin‐2 show that opioid receptor desensitization directly contributes to tolerance and that tolerance and adenylyl cyclase superactivation are two dissociable phenomena (Bohn et al, 1999, 2000). Here, we propose that morphine is unique in that it promotes terminal opioid receptor desensitization by inducing a ...
during 1830s.. In small amounts Salvia divinorum would be prescribed to treat and heal certain illnesses. Examples would be headaches anemia and other unique cases. Salvia divinorum has a few aka names and they are Maria Best Prescription Painkiller For Toothache Pastora sage of seers and Salvia divinorum itself and diviners mint and Sally-D and Lady salvia.. Please choose a different combination. Sorry this product is unavailable. All posts displayed. All items displayed.. While you may utilize more of the product which tastes unpleasant there are other choices available that can fit your lifestyle such as mitragyna speciosa trees for sale wadena capsules for instance. Our website is strictly for Best Prescription Painkiller For Toothache entertainment purposes only. Kratom has not been approved by the FDA and you are responsible for knowing any legalities of the substance in your specific area.. It is very beneficial in conditions and ailments like opiate withdrawal alcohol withdrawal chronic ...
Aims Naltrexone is a competitive opioid antagonist that effectively blocks the action of heroin and other opioid agonists. It has no abuse potential, mild and transient side effects, and thus appears an ideal pharmacotherapy for opioid dependence. Sustained-release naltrexone formulations are now available that provide long-acting opioid blockade. However, further research is warranted, especially data concerning opioid receptor (OR) occupancy on different plasma levels of naltrexone. Positron emission tomography (PET) is a unique imaging modality for studying functional processes in vivo and is used in this study to map OR occupancy on different plasma concentrations of naltrexone in rats. Methods Eleven rats were implanted with a single tablet of 1,95 mg naltrexone. OR occupancy data was acquired at baseline, a few days ...
Phenylethanolamine (sometimes abbreviated PEOH), or β-hydroxyphenethylamine, is a trace amine with a structure similar to those of other trace phenethylamines as well as the catecholamine neurotransmitters dopamine, norepinephrine, and epinephrine. As an organic compound, phenylethanolamine is a β-hydroxylated phenethylamine that is also structurally related to a number of synthetic drugs in the substituted phenethylamine class. In common with these compounds, phenylethanolamine has strong cardiovascular activity and, under the name Apophedrin, has been used as a drug to produce topical vasoconstriction ...
297651240 - EP 0845003 B1 2001-12-05 - NOVEL OPIOID PEPTIDES - [origin: WO9707130A1] This invention relates to novel opioid peptides for the treatment of pain as well as a method for the preparation thereof and pharmaceutically acceptable compositions comprising these peptides. The invention also relates to methods for controlling pain in patients using compositions of the invention and the use of said compounds in the preparation of formulations effective in pain treatment. The peptides of this invention have a high degree of selectivity for the mu -opioid receptor. The peptides of the present invention are particularly well-suited as analgesic agents acting substantially on peripheral mu -opioid receptors. Because these peptides act peripherally, they substantially avoid producing side effects normally associated with central analgesic ...
Opioid agonist treatment is not "substitution." Reporting in the lay press is often sensationalist and inaccurate. But in a leading medical journal accurate non-stigmatizing medical terminology should be preferred as it influences how clinicians and policymakers view the disease opioid use disorder. Illicit heroin and other opioid use produce euphoria and endocrine derangements, and the substances are used compulsively. However, when treatment is given with opioid agonists, there is no euphoria, homeostasis returns and the medications are taken regularly without compulsion, under medical supervision. And these treatments reduce mortality as randomized trials have found (and as have observational studies such as this most recent one).. Unfortunately a major barrier to dissemination of these treatments has been public and even addiction treatment professional misconceptions ...
BioAssay record AID 429160 submitted by ChEMBL: Agonist activity at human delta opioid receptor expressed in CHO cells assessed as stimulation of [35S]GTPgammaS binding by scintillation counting.
In our recent study,3 oxycodone showed weaker activation of the spinal μ-opioid receptors compared with morphine. The mechanisms behind this difference are interesting and will be studied further. In the brain, oxycodone activated the μ-opioid receptors, albeit to a lesser extent than morphine. The reason why oxycodone produces more potent antinociception compared with morphine after systemic administration remains to be clarified. Smith et al. argue that we are suggesting that the analgesic effects of systemic oxycodone are due to oxymorphone. This is not what we concluded. We suggested that the metabolites may have a role in oxycodone-induced analgesia. We agree that the circulating concentrations of oxymorphone after systemic administration of oxycodone are low, as we12-14 and others15 have shown. Because systemic oxycodone causes potent μ-opioid receptor ...
This article reviews pharmacological principles and research strategies aiming at novel opioids with reduced side effects. Basic mechanisms underlying pain, opioid analgesia and other opioid actions are outlined. To illustrate the clinical situation and medical needs, plasticity of opioid receptors, intracellular signaling pathways, endogenous and exogenous opioid receptor ligands, central and per...
Opioids inhibit glutamatergic excitatory transmission from the periphery by activating G-protein coupled opioid receptors in the central terminals of primary-afferent neurons in the spinal substantia gelatinosa, resulting in antinociception. Opioid receptor activation in the peripheral terminals of primary-afferent neurons inhibits the production of action potentials in response to nociceptive stimuli given to the periphery, leading to antinociception. Opioids also exhibit a local anesthetic effect without opioid receptor activation in peripheral nerve fibers. This review article will focus on analgesia and anesthesia produced by the actions of opioids on primary-afferent fibers.
The introduction of tamper-resistant opioid tablets does not have an effect on rates of opioid use or harms at a population level, according to a new study led by the National Drug and Alcohol Research Centre (NDARC) at UNSW Sydney.. A tamper-resistant, difficult to crush formulation of OxyContin, a strong opioid prescribed for chronic pain management, was introduced in Australia in April 2014 in response to growing concerns about its contribution to an increase in opioid use and related harms. The National Opioid Medications Abuse Deterrence (NOMAD) study - the most comprehensive analysis of the impact of tamper-resistant opioid formulations to date - is published in The Lancet Psychiatry journal.. The study used both sales and health data across Australia, as well as survey data from a cohort of 600 people ...
|p|Endomorphins are two endogenous opioid peptides. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH|sub|2|/sub|) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH|sub|2|/sub|) are tetrapeptides with the highest known affinity and specificity for the μ opioid receptor. Endomorph
N-Methyl-N-[3-(trifluoromethyl)benzyl]amine, 97+%, Maybridge Amber Glass Bottle; 1g N-Methyl-N-[3-(trifluoromethyl)benzyl]amine, 97+%, Maybridge Methylthios to Mh...
Salvia divinorum. Common names:. Diviners sage, ska Pastora, hojas de la Pastora, seers sage, la Maria.. The "Just This" Plant. The "Emptiness" plant.. Related species:. Salvia divinorum contains a diterpene, salvinorin. Some Coleus species are rumored to contain similar compounds, but this is still unconfirmed (bioassay reports are mostly negative).. Salvia splendens contains salviarin and splendidin, both diterpenes, and we should expect more from other species. No psychotropic activity has been reported for those but that does not close the case-I heard background whispers of "placebo effect" for years when talking about the powers of dried ska Pastora leaves!. Salvia sonomensis contains a camphorlike substance that is a mild stimulant when smoked. Salvia officinalis contains thujone, constituting in some varieties over fifty percent of the essential oil.. But those plants dont really have anything to do with me.. True.. Taxonomy:. A true sage, like cooking sage. Mint family. There are a ...
Gentaur molecular products has all kinds of products like :search , Neuromi \ Delta Opioid Receptor 358-372, control peptide. \ P10105 for more molecular products just contact us
1. Tramadol analgesic causes respiratory depression that is mainly mediated by opioid receptors. However, Tramadol is a weak opioid receptor agonist, and its metabolites O-desmethyltramadol is only about 1/10 of morphine, and fentanyl is a strong opioid receptor agonist, its potency is about 100 times morphine. When the two together, to be a major contributor to opioid receptors is fentanyl. Pradeep Bhatia was also held this view (1). 2. Tramadol poisoning is overdose. Under normal usage the key is patients renal impairment and CYP2D6 gene duplication (2). We present a case of renal function in patients with normal. Further, in terms of Genotyping of CYP2D6, East Asian and Africans do not exist uitrarapid metabolizers (3).The CYP2D6*10 allele is the most common allele in the Chinese population, and ...
Human Kappa Light Chain, 1 ml. Antibody to the kappa light chain of immunoglobulin is reportedly useful in the identification of leukemias, plasmacytomas, and certain non-Hodgkins lymphomas.
The µ-opioid receptor is the primary target structure of most opioid analgesics and thus responsible for the predominant part of their wanted and unwanted effects. Carriers of the frequent genetic µ-opioid receptor variant N40D (allelic frequency 8.2 - 17 %), coded by the single nucleotide polymorphism A,G at position 118 of the µ-opioid receptor coding gene OPRM1 (OPRM1 118A,G SNP), suffer from a decreased opioid potency and from a higher need of opioid analgesics to reach adequate analgesia. The aim of the present work was to identify the mechanism by which the OPRM1 118A,G SNP decreases the opioid potency and to quantify its effects on the analgesic potency and therapeutic range of opioid ...
The data reported herein provide evidence that hKOR undergoes agonist-dependent ubiquitination, and its ubiquitination regulates, but is not required for, sorting of internalized receptor to degradation pathway. Agonist-promoted ubiquitination of the hKOR, which occurs at Lys residues in the C-terminal domain of the hKOR, is enhanced by hKOR phosphorylation but unchanged by receptor internalization. In addition, agonist-promoted polyubiquitination of the hKOR occurs predominantly as Lys63-linked polyubiquitin chains. To the best of our knowledge, this is the first report that Lys63-linked polyubiquitination of a 7TMR is involved in its down-regulation.. Ubiquitination of the hKOR Regulates, but Is Not Required for, Agonist-Induced hKOR Down-Regulation. Ubiquitination of the hKOR was increased substantially after agonist stimulation. The rapid occurrence of ubiquitination of the hKOR after agonist incubation (30 min) is similar to that reported for several 7TMRs, including ...
The real key to the magic and magic - to disable the internal dialogue. Plant - a valuable teacher in this field. The plant can teach you many things, but disabling the internal dialogue - the "big lesson." The main event. The essence of magic. We smoke the plant - yes, you need to smoke a plant. Preferably smoke extract as need to get "there" as quickly as possible and without problems. All recommendations are reduced to the maximum to choose a dark and quiet place. This is good advice. The plant will give you a clean (free) look at "nagual." In a saturated external stimuli (bright light, noise), this experience may seem annoying or even hell. Many times more annoying than anything you can imagine. You have to realize that plants do not need to annoy you, then what would be the result depends on who and how prezhivaet experience. All due to the nature nagual. It is such that it can easily "knock you off track." The term "you" refers to your "tonal". Your tonal may be horrified by the nagual, ...
Salvia Divinorumis in the news again. 2012 Doomsday Cult followers claim the governments efforts to outlaw the herb is a direct violation of their constitutionally protected religious rights. As...
AWS Lambda is an interesting new service from Amazon Web Services. It allows you to write Lambda Functions and associate these functions with events such as new files appearing in an S3 bucket or new records being written to an Amazon Kinesis stream. The details of how the functions get executed and how they are scaled to meet demand are handled completely by the AWS Lambda service. So, as the developer, you dont have to worry about instances or load balancers or auto scaling groups, etc. It all just happens automatically for you.. Sound too good to be true? Well, there are some caveats. The main one is that the AWS Lambda service is in Preview right now so there are some rough edges. The good news is that AWS has made the service available for testing and evaluation and your input can have a big impact on the future of the service. I encourage you to give it a try.. My first impressions of AWS Lambda (aside from the obvious wow factor) is that the process of creating and deploying a Lambda ...
PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.
Background Opioid analgesics such as morphine and meperidine have been used to control moderate to severe pain for many years. However, these opioids have many side effects, including the development...
Opioids are potent analgesic drugs prescribed to treat pain that ranges from moderate to severe. They have unwanted side effects, can lead to tolerance and dependence, and display addictive properties. Opioids function by acting on mu opioid receptors (MORs) located throughout the CNS. MOR is coupled to inhibitory heterotrimeric G proteins of the Gαi/o family, which have many downstream signaling effects, including inhibition of adenylyl cyclase. Regulators of G protein signaling (RGS) proteins negatively modulate this receptor-mediated G protein signaling. One of the remaining questions regarding the effects of RGS proteins on MOR signaling is which, if any, Gαi/o protein subtype serves as the site of action for RGS protein inhibition of opioid signaling. To evaluate the role of one Gα subunit, Gαo, in the effects of RGS proteins on ...
Previous studies using spinal and supraspinal injections of EMs have reported antinociception in models of acute pain (without sustained tissue injury) or in short-lasting inflammation (1-3 h) (Horvath, 2000; Przewlocki and Przewlocka, 2001). We have now shown that both EMs can also produce antinociception in prolonged inflammatory pain and that this effect is mediated by peripheral opioid receptors. This is supported by our finding that the antinociceptive effects of both intraplantar EMs were blocked by intraplantar application of systemically ineffective doses of opioid receptor antagonists. Peripheral effects of EMs were also found in animals with neuropathic pain (Obara et al., 2004). In our study, both EMs were similarly effective and produced antinociception of comparable duration, in line with findings in other models (Stone et al., 1997; Tseng et al., 2000; Sakurada et al., 2001; Obara et al., ...

Oprk1 - Kappa-type opioid receptor - Mus musculus (Mouse) - Oprk1 gene & proteinOprk1 - Kappa-type opioid receptor - Mus musculus (Mouse) - Oprk1 gene & protein

... but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive ... Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of ... Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. ... G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, ...
more infohttp://www.uniprot.org/uniprot/P33534

14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: design, synthesis...14-O-Heterocyclic-substituted naltrexone derivatives as non-peptide mu opioid receptor selective antagonists: design, synthesis...

Among them, compound 1 exhibited the highest selectivity for the mu opioid receptor over the delta and kappa receptors. These ... These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. ... Naltrexone in MOR-binding pocket: mu opioid receptor model: ribbon and in cyan color; the residues in mu opioid receptor: ball ... Mu opioid receptor antagonists have clinical utility and are important research tools. To develop non-peptide and highly ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/19217280

Etorphine - DrugBankEtorphine - DrugBank

... and kappa opioid receptors. It also has a weak affinity for the ORL1 nociceptin/orphanin FQ receptor. ... Opioid receptor activity. Specific Function. G-protein coupled opioid receptor that functions as receptor for endogenous alpha- ... Also functions as receptor for various synt.... Gene Name. OPRK1. Uniprot ID. P41145. Uniprot Name. Kappa-type opioid receptor ... Gharagozlou P, Hashemi E, DeLorey TM, Clark JD, Lameh J: Pharmacological profiles of opioid ligands at kappa opioid receptors. ...
more infohttps://www.drugbank.ca/drugs/DB01497

Opioid addiction, opioid addiction treatment, and HIV infection.Opioid addiction, opioid addiction treatment, and HIV infection.

Available data indicate that opioid substitution treatment can successfully reduce rates of HIV transmission and that patients ... Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins. ... Tianeptine is an atypical antidepressant which exerts an opioid-like effect on the μ-opioid receptor. There is well documented ... Receptors, Opioid, Mu. A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in ...
more infohttps://www.bioportfolio.com/resources/pmarticle/2201147/Opioid-addiction-opioid-addiction-treatment-and-HIV-infection.html

Replacement of Gln280 by His in TM6 of the human ORL1 receptor increases affinity but reduces intrinsic activity of opioids. -...Replacement of Gln280 by His in TM6 of the human ORL1 receptor increases affinity but reduces intrinsic activity of opioids. -...

... receptor is the G protein-coupled receptor whose amino acid sequence is closest to those of opioid receptors. Residues that are ... Here we have sought to create an opioid binding pocket in the non-opioid ORL1 receptor by replacing residue Gln280 in its TM6 ... which is present in all opioid receptor types but absent in ORL1, appear to play a key role in receptor recognition and/or ... by the corresponding His residue of opioid receptors. The mutation affects neither the affinity of nociceptin - the natural ...
more infohttps://www.semanticscholar.org/paper/Replacement-of-Gln280-by-His-in-TM6-of-the-human-of-Mollereau-Moisand/3b48313a82230a9dfe040a9aec56b31767750897

William Carlezon | Harvard Catalyst Profiles | Harvard CatalystWilliam Carlezon | Harvard Catalyst Profiles | Harvard Catalyst

8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor. Beilstein J Org Chem. 2007 Jan 09; 3:1. PMID: ... Selective ? opioid antagonists nor-BNI, GNTI and JDTic have low affinities for non-opioid receptors and transporters. PLoS One ... Role of kappa-opioid receptors in stress and anxiety-related behavior. Psychopharmacology (Berl). 2013 Oct; 229(3):435-52. PMID ... Ascent of the kappa-opioid receptor in psychopharmacology. Psychopharmacology (Berl). 2010 Jun; 210(2):107-8. PMID: 20401604. ...
more infohttps://connects.catalyst.harvard.edu/Profiles/display/Person/52504

Dynorphin A - WikipediaDynorphin A - Wikipedia

... and delta-opioid receptors; it has the highest binding affinity for the kappa-opioid receptor. Dynorphin 1-13 - Compound ... Dynorphin A is a form of dynorphin and an endogenous opioid peptide with the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg- ... Dynorphin A1-8 is an agonist at the mu-, kappa-, ...
more infohttps://en.wikipedia.org/wiki/Dynorphin_A

Constitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress | eLifeConstitutive activation of kappa opioid receptors at ventral tegmental area inhibitory synapses following acute stress | eLife

Rats exposed to a single stressful event experience days-long constitutive activation of the kappa opioid receptor at ... The orexin 1 receptor modulates kappa opioid receptor function via a JNK-dependent mechanism * JD Robinson ... Although 6β-naltrexol has equivalent affinity for µ and κ ORs, (Wang et al., 2007) our previous work has shown that the block ... Different effects of opioid antagonists on mu-, delta-, and kappa-opioid receptors with and without agonist pretreatment * D ...
more infohttps://elifesciences.org/articles/23785

Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. | Molecular PharmacologyPharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. | Molecular Pharmacology

Opioid agents with abuse potential possess high affinities for the mu receptor. The availability of the cloned receptors will ... and mu receptors using a battery of widely employed opioid agents. Our results suggest that the cloned kappa and mu receptors ... Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.. K Raynor, H Kong, Y Chen, K Yasuda, L ... Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.. K Raynor, H Kong, Y Chen, K Yasuda, L ...
more infohttp://molpharm.aspetjournals.org/content/45/2/330.short

Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. | Molecular PharmacologyPharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors. | Molecular Pharmacology

Opioid agents with abuse potential possess high affinities for the mu receptor. The availability of the cloned receptors will ... and mu receptors using a battery of widely employed opioid agents. Our results suggest that the cloned kappa and mu receptors ... Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.. K Raynor, H Kong, Y Chen, K Yasuda, L ... Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors.. K Raynor, H Kong, Y Chen, K Yasuda, L ...
more infohttp://molpharm.aspetjournals.org/content/45/2/330.long

Opioids for pain management in older adults: Strategies for safe prescribing |  CE Article |  NursingCenterOpioids for pain management in older adults: Strategies for safe prescribing | CE Article | NursingCenter

Opioids are commonly employed to treat pain but mus... ... 18 Other opioid receptor types include the delta, kappa, and ... 18 Although it has a high binding affinity to the mu-opioid receptor, buprenorphine has limited efficacy. This creates a ... Buprenorphine also weakly binds as an antagonist at kappa and delta receptors and is not readily reversed by naloxone.24 There ... Mu-receptor agonist opioids. Morphine and oxycodone are examples of pure mu-agonist opioids because they exert their primary ...
more infohttps://www.nursingcenter.com/cearticle?an=00006205-201702000-00006&

Chapter 11 Major Opioids in Pain Management Flashcards by Olabisi Asimolowo | BrainscapeChapter 11 Major Opioids in Pain Management Flashcards by Olabisi Asimolowo | Brainscape

Study Chapter 11 Major Opioids in Pain Management flashcards from Olabisi Asimolowo ... Buprenorphine has partial agonist activity at mu-opioid receptor and antagonist activity at kappa- and delta-opioid receptors. ... Fentanyl possesses predominantly mu-opioid receptor agonist properties and little affinity for the kappa- and delta-opioid ... lower affinity than morphine for the mu-opioid receptor, which may explain why methadone may have fewer mu-opioid receptor- ...
more infohttps://www.brainscape.com/flashcards/chapter-11-major-opioids-in-pain-manageme-2111420/packs/3681372

Targiniq ER New FDA Drug Approval | CenterWatchTarginiq ER New FDA Drug Approval | CenterWatch

Naloxone antagonizes opioid effects by competing for the mu, kappa, and delta opioid receptor sites with the greatest affinity ... Naloxone is an antagonist acting on mu, kappa, and delta opioid receptors in the brain, spinal cord, and peripheral organs (e.g ... an opioid antagonist. Oxycodone hydrochloride is a full opioid agonist and is relatively selective for the mu receptor, ... For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg/5 mg tablets orally every 12 hours. ...
more infohttp://www.centerwatch.com/drug-information/fda-approved-drugs/drug/100018/

Sage advice?: NC to join 13 states in outlawing Salvia divinorum | ScienceBlogsSage advice?: NC to join 13 states in outlawing Salvia divinorum | ScienceBlogs

... and sigma receptors. One in particular, dubbed "herkinorin", has show very strong selective affinity for the mu opioid receptor ... 1) Kappa opioid receptor (KOR) agonists are dysphoric. (See Land et al, 2008; Pfeiffer et al., 1986) Ive listened to some ... Really great post! As someone who has spent their post-doc actively investigating the Kappa opioid receptor I find the ban in ... Several large pharmaceutical companies have Kappa-opioid receptor projects ongoing for using KOR as a target for the above ...
more infohttps://scienceblogs.com/terrasig/2009/06/14/sage-advice-nc-to-join-13-stat

Differential Expression and Sensitivity of Presynaptic and Postsynaptic Opioid Receptors Regulating Hypothalamic...Differential Expression and Sensitivity of Presynaptic and Postsynaptic Opioid Receptors Regulating Hypothalamic...

1994) Mu, delta, and kappa opioid receptor mRNA expression in the rat CNS: an in situ hybridization study. J Comp Neurol 350: ... However, these receptors have varying affinities for endogenous ligands found in the arcuate, with beta-endorphin being ... Opioids can exert their effects through multiple classes of opioid receptors, including mu, delta, and kappa receptors (MOR, ... Possible interaction between mu and kappa opioid receptors. Opioid receptors can form functional dimers in various combinations ...
more infohttps://www.jneurosci.org/content/31/1/281?ijkey=a31c5ffad6ee9de24160c68c0c348abc881fdc02&keytype2=tf_ipsecsha

Plus itPlus it

... the two endomorphins also displayed very poor affinities for delta and kappa1receptors and high affinity for both mu receptor ... As noted with most opioids, the affinity of these compounds for themu1 receptors was greater than for themu2 receptor. We also ... 1989) Kappa opiate receptor multiplicity: Evidence for two U50,488-sensitive kappa1 subtypes and a novel kappa3 subtype. J ... The high affinity of the two endomorphins for mu receptors was confirmed in competition studies against the cloned mu receptor ...
more infohttp://jpet.aspetjournals.org/content/286/2/1007

Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β...Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β...

reported that it acted nonselectively on mu- and delta opioid receptors, while its kappa opioid receptor affinity was ... a kappa opioid receptor (Oprk1) clone. MOR-1. a mu opioid receptor (Oprm1) clone. norBNI. norbinaltorphimine. NTI. naltrindole ... 45 2 exhibited no affinity appreciable affinity at these receptors (Ki , 10 μM). 3 had poor affinity at α2A adrenergic receptor ... delta opioid receptor gene (Oprd1), and kappa opioid receptor gene (Oprk1) (Table 3). These probes have been previously ...
more infohttp://pubmedcentralcanada.ca/pmcc/articles/PMC5344672/

Opioid antagonist - WikipediaOpioid antagonist - Wikipedia

An opioid antagonist, or opioid receptor antagonist, is a receptor antagonist that acts on one or more of the opioid receptors ... "Discovery of the first small-molecule opioid pan antagonist with nanomolar affinity at mu, delta, kappa, and nociceptin opioid ... Many of them also bind to the κ-opioid receptor (KOR) and/or δ-opioid receptor (DOR), where they variously behave as ... The more dramatic result of naloxone versus naltrexone is suspected to be due to different opioid receptor affinity/selectivity ...
more infohttps://en.wikipedia.org/wiki/Opioid_antagonist

Interactions between kappa and mu opioid receptor agonists: effects of the ratio of drugs in mixtures | Springer for Research &...Interactions between kappa and mu opioid receptor agonists: effects of the ratio of drugs in mixtures | Springer for Research &...

... and mu opioid receptor agonists continue to be prescribed despite well-documented adverse effects. Kappaopioid receptor ... Porreca F, Mosberg HI, Hurst R, Hruby VJ, Burks TF (1984) Roles of mu, delta and kappa opioid receptors in spinal and ... Walker EA, Zernig G, Young AM (1998) In vivo apparent affinity and efficacy estimates for mu opiates in a rat tail-withdrawal ... and mu opioid receptor agonists continue to be prescribed despite well-documented adverse effects. Kappa opioid receptor ...
more infohttps://rd.springer.com/article/10.1007%2Fs00213-018-4920-x

enadoline | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGYenadoline | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY

Radioligand-dependent discrepancy in agonist affinities enhanced by mutations in the kappa-opioid receptor. Mol Pharmacol, 50: ... Design and synthesis of novel dimeric morphinan ligands for kappa and micro opioid receptors. J Med Chem, 46: 5162-5170. [PMID: ... CI-977, a novel and selective agonist for the kappa-opioid receptor. Br. J. Pharmacol., 101 (1): 183-9. [PMID:2178014] ...
more infohttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=refs&ligandId=1646

Improving the accuracy of high-throughput protein-protein affinity prediction may require better training data | BMC...Improving the accuracy of high-throughput protein-protein affinity prediction may require better training data | BMC...

... their associated binding affinities and experimental conditions were obtained from different binding affinity and structural ... We recently found that protein-DNA/RNA affinity can also be predicted with high accuracy using extensions of existing ... Here we evaluate a range of potential factors that may interfere with accurate protein-protein affinity prediction. We find ... We also highlight a number of potential errors in large structure-affinity databases, which could affect both model training ...
more infohttps://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1533-z

Antinociceptive activity of thiazole-containing cyclized DAMGO and Leu-(Met) enkephalin analogs - Organic & Biomolecular...Antinociceptive activity of thiazole-containing cyclized DAMGO and Leu-(Met) enkephalin analogs - Organic & Biomolecular...

This study sought to increase the oral bioavailability of opioid peptides by cyclization, using Hantzsch-based macrocyclization ... Numerous studies demonstrate the promise of opioid peptides as analgesics, but poor oral bioavailability has limited their ... Compounds demonstrated modest affinity but high selectivity for the mu, delta, and kappa opioid receptors (MOR, DOR and KOR), ... Opioid receptor affinity and selectivity for compounds in each series were assessed in vitro with radioligand competition ...
more infohttps://pubs.rsc.org/en/Content/ArticleLanding/2019/OB/C9OB00882A

Kratom and the FDA  |  In the PipelineKratom and the FDA | In the Pipeline

... micromolar affinity) at the kappa receptor. The other related alkaloids were basically inactive, except the 7-hydroxy, which is ... Naloxone, a life-saving opioid antagonist binds to mu-opioid receptors, but its not scheduled. ... The paper referenced above finds that mitragynine is a partial agonist at the mu-opioid receptor and a competitive antagonist ( ... The point is that yes, kratoms active constituents do indeed act on opioid receptors - possibly in a way that would ...
more infohttp://blogs.sciencemag.org/pipeline/archives/2018/02/08/kratom-and-the-fda

Salvia Divinorum: Uses, Side Effects, Interactions, Dosage, and WarningSalvia Divinorum: Uses, Side Effects, Interactions, Dosage, and Warning

... diterpenoids isolated from the leaves of Salvia divinorum and their binding affinities for human kappa opioid receptors. Bioorg ... Fantegrossi, W. E., Kugle, K. M., Valdes, L. J., III, Koreeda, M., and Woods, J. H. Kappa-opioid receptor-mediated effects of ... on kappa opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo. J Pharmacol Exp Ther 2005;312 ... a structurally unique kappa opioid receptor agonist. Pharmacol Biochem Behav. 2006;83(1):109-113. View abstract. ...
more infohttps://www.webmd.com/vitamins/ai/ingredientmono-1043/salvia-divinorum

Salvia divinorum | Salvia | The Salvia divinorum Research and Information Center: The most comprehensive resource for...Salvia divinorum | Salvia | The Salvia divinorum Research and Information Center: The most comprehensive resource for...

8-epi-Salvinorin B: Crystal Structure and Affinity at the Kappa Opioid Receptor.. by Munro TA, Duncan KK, Staples RJ, Xu W, Liu ... Cross-Talk Between Kappa-Opioid and Cannabinoid CB1 Receptors.. by Capasso R, Borrelli F, Cascio MG, Aviello G, Huben K, ... A Select Set of Opioid Ligands Induce Up-Regulation by Promoting the Maturation. and Stability of the Rat Kappa Opioid Receptor ... An Opioid Agonist That Does Not Induce Mu-Opioid Receptor Arrestin Interactions or Receptor Internalization.. by Groer CE, ...
more infohttp://www.sagewisdom.org/index.html
  • The compound itself is remarkable - it is the first, naturally-occurring non-nitrogenous ligand ever identified for an opioid receptor (unlike morphine and codeine, for example. (scienceblogs.com)
  • Functional inactivation of the nociceptin receptor by alanine substitution of glutamine 286 at the C terminus of transmembrane segment VI: evidence from a site-directed mutagenesis study of the ORL1 receptor transmembrane-binding domain. (semanticscholar.org)
  • It does so by activating a protein on the surface of VTA neurons called the kappa opioid receptor (κOR for short). (elifesciences.org)
  • However, both intrinsic properties and synaptic inputs contribute to the regulation of POMC neurons such that attributing an autoregulatory role to opioids must include consideration of opioid receptor localization and sensitivity at both presynaptic and postsynaptic sites. (jneurosci.org)
  • The results may help explain why it has been difficult to clearly discern the role that opioids play in the regulation of food intake and other processes involving POMC neurons. (jneurosci.org)
  • Thus, the goal of the current study was to determine the distribution and relative contribution of presynaptic and postsynaptic opioid receptors in the regulation of POMC neurons. (jneurosci.org)
  • The data demonstrate that all three opioid receptors examined can act presynaptically to inhibit transmitter release, but only MORs directly inhibit POMC neurons via a postsynaptic mechanism. (jneurosci.org)
  • 4 However, opioids and other medications used to treat pain must be used with caution in older adults due to the increased risk of serious adverse drug events (ADEs), including respiratory depression, central nervous system depression, falls and fractures, gastrointestinal (GI) bleeding, sedation, delirium, and cognitive changes. (nursingcenter.com)
  • Dart RC, Surratt HL, Cicero TJ, Parrino MW, Severtson SG, Bucher-Bartelson B, Green JL (2015) Trends in opioid analgesia abuse and mortality in the United States. (springer.com)
  • These compounds showed subnanomolar-to-nanomolar binding affinity for the mu opioid receptor. (nih.gov)
  • When at Case Western Reserve University, Bryan Roth's group was supported by the National Institute for Mental Health to create a screening panel of neurochemical transporters and G-protein-coupled receptors for identifying the mechanism(s) of action of novel compounds. (scienceblogs.com)
  • Briggs SL, Rech RH, Sawyer (1998) Kappa antinociceptive activity of spiradoline in the cold-water tail-flick assay in rats. (springer.com)
  • If adverse effects of each constituent drug are reduced or avoided, then kappa:mu mixtures might be advantageous to mu opioids alone. (springer.com)
  • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Targiniq ER for use in patients for whom alternative treatment options are inadequete. (centerwatch.com)
  • The FDA approval of Targiniq ER was based on one 12-week, randomized, double-blind, placebo-controlled clinical trial in opioid-experienced patients with uncontrolled moderate to severe chronic low back pain. (centerwatch.com)
  • Available data indicate that opioid substitution treatment can successfully reduce rates of HIV transmission and that patients receiving such treatment can adhere to therapies for HIV, hepatitis C, and tuberculosis infection. (bioportfolio.com)
  • Integration of opioid substitution treatment into the HIV clinic setting can make such treatment easier and improve retention in treatment. (bioportfolio.com)
  • Attenuated dopamine receptor signaling in nucleus accumbens core in a rat model of chemically-induced neuropathy. (harvard.edu)
  • With the exception of the rat β1 and β2 adrenergic and bovine dopamine transporter (DAT) all of the assays were performed with cloned human receptors heterologously expressed (see Materials and Methods and supporting information on the PNAS web site for details). (scienceblogs.com)
  • Shown is the mean percent inhibition of radioligand binding or functional activity (metabotropic glutamate receptors only) to 50 receptors and transporters for LSD (yellow bars) and Salvinorin A (red bars) tested at 10 µM. (scienceblogs.com)
  • Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. (uniprot.org)
  • In addition to differential expression of opioid receptors at presynaptic and postsynaptic sites, the data indicate that there is a significant difference in the sensitivity of presynaptic and postsynaptic MORs. (jneurosci.org)
  • This differential sensitivity adds an unexpected component of opioid-dependent feedback regulation, where low levels of opioid receptor activation would likely disinhibit POMC neuron activity and higher concentrations would result in an overall inhibition. (jneurosci.org)
  • After a stressful event, the receptors are said to have become constitutively active, and blocking this constitutive activity prevents stress from inducing drug-seeking behavior. (elifesciences.org)