Ganglionic Stimulants: Agents that mimic neural transmission by stimulation of the nicotinic receptors on postganglionic autonomic neurons. Drugs that indirectly augment ganglionic transmission by increasing the release or slowing the breakdown of acetylcholine or by non-nicotinic effects on postganglionic neurons are not included here nor are the nonspecific cholinergic agonists.Vesicular Monoamine Transport Proteins: A family of vesicular amine transporter proteins that catalyze the transport and storage of CATECHOLAMINES and indolamines into SECRETORY VESICLES.Vesicular Biogenic Amine Transport Proteins: Integral membrane proteins of the LIPID BILAYER of SECRETORY VESICLES that catalyze transport and storage of biogenic amine NEUROTRANSMITTERS such as ACETYLCHOLINE; SEROTONIN; MELATONIN; HISTAMINE; and CATECHOLAMINES. The transporters exchange vesicular protons for cytoplasmic neurotransmitters.Neurotransmitter Transport Proteins: Membrane transport proteins found predominately in NEURONS and neuroendocrine cells that facilitate neurotransmitter transport. They include two distinct families of proteins that transport NEUROTRANSMITTERS across the PLASMA MEMBRANE and that transport NEUROTRANSMITTERS into SECRETORY VESICLES.Neurochemistry: The study of the composition, chemical structures, and chemical reactions of the NERVOUS SYSTEM or its components.Lobelia: A plant genus of the family CAMPANULACEAE used medicinally and is a source of LOBELINE.Nicotinic Agonists: Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.3,4-Dihydroxyphenylacetic Acid: A deaminated metabolite of LEVODOPA.Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.Libraries, Digital: Libraries in which a major proportion of the resources are available in machine-readable format, rather than on paper or MICROFORM.Tetrabenazine: A drug formerly used as an antipsychotic and treatment of various movement disorders. Tetrabenazine blocks neurotransmitter uptake into adrenergic storage vesicles and has been used as a high affinity label for the vesicle transport system.AzocinesLobeline: An alkaloid that has actions similar to NICOTINE on nicotinic cholinergic receptors but is less potent. It has been proposed for a variety of therapeutic uses including in respiratory disorders, peripheral vascular disorders, insomnia, and smoking cessation.Respiratory System Agents: Drugs used for their effects on the respiratory system.QuinolizinesDopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.Dopamine Agents: Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke.Amphetamine-Related Disorders: Disorders related or resulting from use of amphetamines.Aconitine: A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has antiinflammatory and antineuralgic properties.Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters.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.Psychomotor Agitation: A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.Medial Forebrain Bundle: A complex group of fibers arising from the basal olfactory regions, the periamygdaloid region, and the septal nuclei, and passing to the lateral hypothalamus. Some fibers continue into the tegmentum.Dopamine: One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.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.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool.Alkaloids: Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)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)Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Dopamine Uptake Inhibitors: Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids.Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors.Central Nervous System Depressants: A very loosely defined group of drugs that tend to reduce the activity of the central nervous system. The major groups included here are ethyl alcohol, anesthetics, hypnotics and sedatives, narcotics, and tranquilizing agents (antipsychotics and antianxiety agents).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.Norepinephrine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. It regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS.EstersSynaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates.Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE.Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents.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)Corpus Striatum: Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.TritiumCocaine: 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.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.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.Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (ANTIBIOTIC PROPHYLAXIS) and anti-anxiety agents. It does not include PREANESTHETIC MEDICATION.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.Pertussis 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.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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Lipopolysaccharides: Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Virulence Factors, Bordetella: A set of BACTERIAL ADHESINS and TOXINS, BIOLOGICAL produced by BORDETELLA organisms that determine the pathogenesis of BORDETELLA INFECTIONS, such as WHOOPING COUGH. They include filamentous hemagglutinin; FIMBRIAE PROTEINS; pertactin; PERTUSSIS TOXIN; ADENYLATE CYCLASE TOXIN; dermonecrotic toxin; tracheal cytotoxin; Bordetella LIPOPOLYSACCHARIDES; and tracheal colonization factor.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.Drug Synergism: The action of a drug in promoting or enhancing the effectiveness of another drug.Injections, Intraventricular: Injections into the cerebral ventricles.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.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.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Mice, Inbred C57BLKinetics: The rate dynamics in chemical or physical systems.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.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.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.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.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Indoles: Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.Piperidines: A family of hexahydropyridines.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.Reperfusion Injury: Adverse functional, metabolic, or structural changes in ischemic tissues resulting from the restoration of blood flow to the tissue (REPERFUSION), including swelling; HEMORRHAGE; NECROSIS; and damage from FREE RADICALS. The most common instance is MYOCARDIAL REPERFUSION INJURY.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Injections, Intravenous: Injections made into a vein for therapeutic or experimental purposes.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Imidazoles: Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).Bradykinin: A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Mice, Inbred ICRSerotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Mice, Inbred BALB CAcetylcysteine: The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.Atropine: An alkaloid, originally from Atropa belladonna, but found in other plants, mainly SOLANACEAE. Hyoscyamine is the 3(S)-endo isomer of atropine.Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.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.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.Injections, Intraperitoneal: Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.Cytoprotection: The process by which chemical compounds provide protection to cells against harmful agents.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Dinoprostone: The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa.Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Behavior, Animal: The observable response an animal makes to any situation.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi.Dexamethasone: An anti-inflammatory 9-fluoro-glucocorticoid.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Mitogen-Activated Protein Kinases: A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).PiperazinesBrain: 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.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.Colforsin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Oligopeptides: Peptides composed of between two and twelve amino acids.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent.Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)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.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.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.-.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Injections, Spinal: Introduction of therapeutic agents into the spinal region using a needle and syringe.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Type C Phospholipases: A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.Cell Adhesion: Adherence of cells to surfaces or to other cells.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Vasoconstrictor Agents: Drugs used to cause constriction of the blood vessels.Isoquinolines: A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)Gastric Mucosa: Lining of the STOMACH, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. The surface cells produce MUCUS that protects the stomach from attack by digestive acid and enzymes. When the epithelium invaginates into the LAMINA PROPRIA at various region of the stomach (CARDIA; GASTRIC FUNDUS; and PYLORUS), different tubular gastric glands are formed. These glands consist of cells that secrete mucus, enzymes, HYDROCHLORIC ACID, or hormones.Free Radical Scavengers: Substances that influence the course of a chemical reaction by ready combination with free radicals. Among other effects, this combining activity protects pancreatic islets against damage by cytokines and prevents myocardial and pulmonary perfusion injuries.Acetylcholine: A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.Sulfonamides: A group of compounds that contain the structure SO2NH2.Pyrrolidinones: A group of compounds that are derivatives of oxo-pyrrolidines. A member of this group is 2-oxo pyrrolidine, which is an intermediate in the manufacture of polyvinylpyrrolidone. (From Merck Index, 11th ed)Drug Administration Schedule: Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience.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.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Fenclonine: A selective and irreversible inhibitor of tryptophan hydroxylase, a rate-limiting enzyme in the biosynthesis of serotonin (5-HYDROXYTRYPTAMINE). Fenclonine acts pharmacologically to deplete endogenous levels of serotonin.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Angiotensin II: An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.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.Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects.Adenosine: A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.Bronchoconstriction: Narrowing of the caliber of the BRONCHI, physiologically or as a result of pharmacological intervention.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Ischemic Preconditioning, Myocardial: Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Caspase 3: A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Superoxides: Highly reactive compounds produced when oxygen is reduced by a single electron. In biological systems, they may be generated during the normal catalytic function of a number of enzymes and during the oxidation of hemoglobin to METHEMOGLOBIN. In living organisms, SUPEROXIDE DISMUTASE protects the cell from the deleterious effects of superoxides.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.Flavonoids: A group of phenyl benzopyrans named for having structures like FLAVONES.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
... is one of the simplest quaternary ammonium salts, with four methyl groups tetrahedrally attached to the central N. The chemical formula (CH3)4N+Cl− is often abbreviated further as Me4N+Cl−. It is a hygroscopic colourless solid that is soluble in water and polar organic solvents. Tetramethylammonium chloride is a major industrial chemical,[1] being used in such processes as hydrofracking.[2] In the laboratory, it has fewer synthetic chemical applications than quaternary ammonium salts containing longer N-alkyl substituents, which are used extensively as phase-transfer catalysts. ...
The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membrane of synaptic vesicles of presynaptic neurons. It acts to transport monoamine neurotransmitters - such as dopamine, serotonin, norepinephrine, epinephrine, and histamine - into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import. Pharmaceutical drugs that target VMATs have possible applications for many conditions, leading to a plethora of biological research. These applications include hypertension, drug addiction, psychiatric disorders, Parkinson's disease, and other neurological disorders. Many drugs that target VMAT act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing. The two VMAT isoforms are: VMAT1 VMAT2 Monoamines transported by VMATs are mainly ...
... is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand, some parts of Europe and in the United States as an orphan drug. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenazine to treat chorea associated with Huntington's disease. Although other drugs had been used "off label," tetrabenazine was the first approved treatment for Huntington's disease in the U.S. The compound has been known since the 1950s. Tetrabenazine is used as a treatment, but not as a cure, for hyperkinetic disorders such as: Huntington's disease - specifically, the chorea associated with it Tourette syndrome and other tic disorders Tardive dyskinesia, a serious and sometimes irreversible side effect of long-term use of many antipsychotics, mainly typical antipsychotics Hemiballismus, spontaneous flinging limb movements due to contra-lateral subthalamic nucleus damage The ...
... means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain structures facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that ...
The God gene hypothesis proposes that human spirituality is influenced by heredity and that a specific gene, called vesicular monoamine transporter 2 (VMAT2), predisposes humans towards spiritual or mystic experiences. The idea has been proposed by geneticist Dean Hamer in the 2004 book called The God Gene: How Faith is Hardwired into our Genes. The God gene hypothesis is based on a combination of behavioral genetic, neurobiological and psychological studies. The major arguments of the hypothesis are: (1) spirituality can be quantified by psychometric measurements; (2) the underlying tendency to spirituality is partially heritable; (3) part of this heritability can be attributed to the gene VMAT2; (4) this gene acts by altering monoamine levels; and (5) spirituality provides an evolutionary advantage by providing individuals with an innate sense of optimism. According to the God Gene hypothesis, spirituality has a genetic component, of which (VMAT2) comprises one component by contributing to ...
... refers to the immediate and deleterious effects of cocaine on the body. Although cocaine intoxication and cocaine dependence can be present in the same individual, these syndromes present with different symptoms. Cocaine increases alertness, feelings of well-being, euphoria, energy, competence, sociability, and sexuality. Common side effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause insomnia, anorexia, tachycardia, hallucinations, and paranoid delusions. Possible lethal side effects include rapid heartbeat, abnormal heart rhythms, tremors, convulsions, markedly increased core temperature, renal failure, heart attack, stroke and heart failure. Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage ...
The synthesis of 5-HT, in EC cells, is catalyzed by the enzyme tryptophan hydroxylase 1 (TpH1) from the amino acid L-tryptophan. The reaction proceeds in two stages with an initial rate limiting step involving the conversion of L-tryptophan to 5-hydroxytryptophan (5-HTP). Following conversion to 5-HTP, the non-rate limiting L-amino acid decarboxylase converts 5-HTP to 5-HT by decarboxylation. Following synthesis, 5-HT is then stored in vesicles by vesicular monoamine transporter 1 close to the basal margin of the cell for eventual secretion.[2] Release of the vesicles occurs after chemical, neurological or mechanical stimulation of the EC cells and is predominantly calcium dependent, suggesting excretion via exocytosis. The combined effect of increased calcium flux and a liberation of stored calcium within the cell changes the cell potential triggering release of the 5-HT vesicles.[13] The vesicles pass from the basal margin into the surrounding lamina propria for interaction with nearby nerve ...
The norepinephrine transporter (NET), also known as solute carrier family 6 member 2 (SLC6A2), is a protein that in humans is encoded by the SLC6A2 gene. NET is a monoamine transporter and is responsible for the sodium-chloride (Na+/Cl−)-dependent reuptake of extracellular norepinephrine (NE), which is also known as noradrenaline. NET can also reuptake extracellular dopamine (DA). The reuptake of these two neurotransmitters is essential in regulating concentrations in the synaptic cleft. NETs, along with the other monoamine transporters, are the targets of many antidepressants and recreational drugs. In addition, an overabundance of NET is associated with ADHD. There is evidence that single-nucleotide polymorphisms in the NET gene (SLC6A2) may be an underlying factor in some of these disorders. The norepinephrine transporter gene, SLC6A2 is located on human chromosome 16 locus 16q12.2. This gene is encoded by 14 exons. Based on the nucleotide and amino acid sequence, the NET transporter ...
... (also known by trade names Raudixin, Serpalan, Serpasil) is an indole alkaloid, antipsychotic, and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic symptoms, although because of the development of better drugs for these purposes and because of its numerous side-effects, it is rarely used today. The antihypertensive actions of reserpine are a result of its ability to deplete catecholamines (among other monoamine neurotransmitters) from peripheral sympathetic nerve endings. These substances are normally involved in controlling heart rate, force of cardiac contraction and peripheral vascular resistance. Reserpine-mediated depletion of monoamine neurotransmitters in the synapses is often cited as evidence to the theory that depletion of the monoamine neurotransmitters causes subsequent depression in humans (c.f. monoamine hypothesis). However, this claim is not without controversy. The reserpine-induced depression is considered ...
그러나, 다른 이론은 monoamine의 정지가 총 민감성을 회복하기 위해 뇌의 monoamine 수용기를 되찾을 수 있게 하기 위해 요구 되는 것이라고 주장한다. 만약 렘 수면이 반복적으로 중단된 사람은 다음 기회에 Rebound sleep 으로 더 긴 렘 수면을 보상 받을 것이다. 그 유일한 치료방법은 일찍 자는 것이다. 특정 신경전달물질의 불균형과 관계 되어 나타나는 우울증의 경우일 때, 예리한 렘 수면 손실은 그 특정 우울증을 야기한다고 주장된다. 그러나 이것은 증명되지 않았다. 화학적 불균형의 가설을 증명할 실험도 알려지지 않았다. 대부분 항 우울증은 monoamine영향으로 인해 선택적으로 렘 수면을 제어한다. 그러나 그 효과는 오랜 기간 지나면 효과가 감소한다. 일부 연구자들은 렘 수면이 조류와 포유류의 생존을 위한 중요 기능을 돕는 것과 같은 복잡한 과정의 ...
The vesicular monoamine transporter (VMAT) is a transport protein integrated into the membrane of synaptic vesicles of presynaptic neurons. It acts to transport monoamine neurotransmitters - such as dopamine, serotonin, norepinephrine, epinephrine, and histamine - into the vesicles, which release the neurotransmitters into synapses as chemical messages to postsynaptic neurons. VMATs utilize a proton gradient generated by V-ATPases in vesicle membranes to power monoamine import. Pharmaceutical drugs that target VMATs have possible applications for many conditions, leading to a plethora of biological research. These applications include hypertension, drug addiction, psychiatric disorders, Parkinson's disease, and other neurological disorders. Many drugs that target VMAT act as inhibitors and alter the kinetics of the protein. Much research regarding the effects of altered VMATs on biological systems is still ongoing. The two VMAT isoforms are: VMAT1 VMAT2 Monoamines transported by VMATs are mainly ...
The God gene hypothesis proposes that human spirituality is influenced by heredity and that a specific gene, called vesicular monoamine transporter 2 (VMAT2), predisposes humans towards spiritual or mystic experiences. The idea has been proposed by geneticist Dean Hamer in the 2004 book called The God Gene: How Faith is Hardwired into our Genes. The God gene hypothesis is based on a combination of behavioral genetic, neurobiological and psychological studies. The major arguments of the hypothesis are: (1) spirituality can be quantified by psychometric measurements; (2) the underlying tendency to spirituality is partially heritable; (3) part of this heritability can be attributed to the gene VMAT2; (4) this gene acts by altering monoamine levels; and (5) spirituality provides an evolutionary advantage by providing individuals with an innate sense of optimism. According to the God Gene hypothesis, spirituality has a genetic component, of which (VMAT2) comprises one component by contributing to ...
... refers to the immediate and deleterious effects of cocaine on the body. Although cocaine intoxication and cocaine dependence can be present in the same individual, these syndromes present with different symptoms. Cocaine increases alertness, feelings of well-being, euphoria, energy, competence, sociability, and sexuality. Common side effects include anxiety, increased temperature, paranoia, restlessness, and teeth grinding. With prolonged use, the drug can cause insomnia, anorexia, tachycardia, hallucinations, and paranoid delusions. Possible lethal side effects include rapid heartbeat, abnormal heart rhythms, tremors, convulsions, markedly increased core temperature, renal failure, heart attack, stroke and heart failure. Depression with suicidal ideation may develop in heavy users. Finally, a loss of vesicular monoamine transporters, neurofilament proteins, and other morphological changes appear to indicate a long-term damage to dopamine neurons. Chronic intranasal usage ...
... in which no lobeline pretreatment was administered prior to the session.. Surmountability of Lobeline Pretreatment.. To ... the effect of acute lobeline pretreatment on sucrose reinforced responding, the effect of repeated lobeline pretreatment ond- ... Repeated Lobeline Pretreatment.. To determine whether lobeline altered d-methamphetamine (0.05 mg/kg/infusion) self- ... Acute Lobeline Pretreatment.. To determine whether lobeline altered d-methamphetamine self-administration, rats were pretreated ...
The effects of lobeline pretreatment on METH-induced hyperthermia. Lobeline (10 mg/kg) or saline (1 ml/kg) was injected 15 min ... Lobeline pretreatment and METH-induced vesicular VMAT-2 immunoreactivity 1 h after METH. Lobeline (10 mg/kg) or saline was ... A and B, effects of lobeline pretreatment on long-term METH-induced striatal DA (A) and 5-HT (B) depletions. Lobeline (10 mg/kg ... Lobeline pretreatment did not affect METH-induced dopamine release but attenuated the decreases in VMAT-2 after METH and the ...
... the present study assessed the effect of lobeline pretreatment on nicotine-induced hyperactivity and sensitization. For 12 ... Lobeline attenuated the induction of sensitization to nicotine 1 day, but not 28 days, after the cessation of lobeline ... indicating that lobeline acts as a nicotinic receptor antagonist. To determine whether lobeline also inhibits the effects of ... Lobeline attenuates locomotor stimulation induced by repeated nicotine administration in rats. Share this page: ...
Bevantolol increased correspondingly the heart rate both when given him alone and after pretreatment combined with lobeline. ...
Swaby-Lobeline Pump Company Positive Displacement - Bio Solid Transfer - Sludge Removal SWABY LOBELINE - Booth 1253 921 Seaco ... Sludge Pretreatment3. Chemicals / Chemical Handling Equipment. *Boiler Chemicals1. *Chemical / Polymer Feed Equip12 ...
Smokers find that the lobeline in Lobelia helps reduce nicotine craving and therefore assists in withdrawal. Although Samuel ... Malsch U, Keiser M. Efficacy of Kava Kava in the treatment of non-psychotic anxiety, following pretreatment with ...
However, an ex vivo study demonstrated that the activity of rat hepatic CYP2E1 was significantly increased by pretreatment of ... These results are consistent with the view that lobeline modulates brain reinforcement processes. ...
purposes in end increase, steroids prednisone pregnancy drug, gain and lobe line were observed. In our mice, we employed time ... Study may be initiated in symptoms much to farone; pretreatment same for 2-3 reactions, prezzo with a pregnancy prednisone ...
An active ingredient in the lobelia plant, lobeline, is similar to nicotine in its effect on the body. ... Lobelia siphiliticata Blue Lobelia seeds are very small and will germinate without pretreatment. ... OF INTEREST: Lobelia inflata is the source of the alkaloid lobeline used medicinally as a respiratory stimulant and in ...
No reports of lobeline alleviating the dysfunctions in PD have appeared breakkut date. Or is that too long. Solange kein ... Retention time: estriol about 19 min; impurity A about 21 min; if the retention times increase, recovery to pretreatment levels ...
Patent 6087350: Use of pretreatment chemicals to enhance efficacy of cytotoxic agents. (DRUG, BIO-AFFECTING AND BODY TREATING ... Patent 6087376: Use of lobeline compounds in the treatment of central nervous system diseases and pathologies. (DRUG, BIO- ...
The aboveground parts of these plants contain the alkaloid lobeline. Some lobelias are cultivated as ornamentals. L. erinus is ... asthma with and without pretreatment of 0.75 mg. *Asthma Without Acute Bronchospasm ... The dried leaves and stems of Indian tobacco and sometimes of other species furnish medicinal lobelia, the source of lobeline, ... Leaves taste like tobacco and contains a non-addictive nicotine-like substance called Lobeline, so chewing them helps people ...
Pretreatment studies were done with H2SO4, followed by enzymatic saccharification. The efficiency of the process was evaluated ... The stems contained a mixture of lobeline (1), norlobelanidine (2), 1-(1-(2-hydroxy-2-phenylethyl)-1-methylpiperidin) butane-2- ... Dilute acid pretreatment and enzymatic hydrolysis of sorghum biomass for sugar recovery-A statistical approach. ... The cellulose content in the solid portion obtained after pretreatment using optimised conditions was found to be increased by ...
Effects of fluoride pretreatment in vitro on human teeth exposed to citrus juice. In fact, the degree of inflammation and the ... Analyses of changes in average PR breakpoint scores between the 2 sessions revealed that lobeline significantly suppressed PR ...
NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on ... lobeline, and lobelanine, have been obtained from Lobelia chinensis Lour. Experimental studies and clinical applications have ... NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on ... pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase ...
J. Pharmacol., 114:708-14 (1995); Lecci, A., et al., Capsaicin Pretreatment Does Not Alter Rat Urinary Bladder Motor Responses ... lobeline, RJR-2403, SIB-1765F, GTS-21, ABT-418), α2-adrenergic receptor agonists [e.g., clonidine, dexmedetomidine, ... This evoked release was effectively inhibited by ketoprofen (81%) but minimally affected by pre-treatment with nifedipine (12 ... demonstrates the effect of ketoprofen pretreatment on acetic acid-induced bladder hyperactivity from Example V. ...
... mepyramine binding were not changed by histamine pretreatment. … ...
... were changed by histamine pretreatment: two types of changes, i.e. a rightward shift in the monophasic curve or an increase in ...
The antitussive effects of dextromethorphan were significantly and dose-dependently reduced by pretreatment with rimcazole, a ... Preferred compounds having particularly potent inhibitory activities include yohimbine, haloperidol, ajmaline, lobeline, and ... The antitussive effect dextromethorphan was also significantly reduced by pretreatment with methysergide, but not ketanserin, ... as many experimental studies used pretreatment paradigms. However, researchers have reported promising findings of protective ...
  • The dried leaves and stems of Indian tobacco and sometimes of other species furnish medicinal lobelia, the source of lobeline, which is used as a respiratory stimulant but is poisonous in overdose as are the roots. (thefreedictionary.com)
  • In contrast, lobeline does not produce conditioned place preference ( Fudala and Iwamoto, 1986 ) and does not engender robust self-administration in mice ( Rasmussen and Swedburg, 1998 ). (aspetjournals.org)