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.Receptor, Adenosine A2A: A subclass of adenosine A2 receptors found in LEUKOCYTES, the SPLEEN, the THYMUS and a variety of other tissues. It is generally considered to be a receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Receptor, Adenosine A1: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of tissues including the BRAIN and DORSAL HORN NEURONS. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Adenosine A2 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.Purinergic P1 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P1 RECEPTORS.Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of ADENOSINE to INOSINE with the elimination of AMMONIA.Adenosine A1 Receptor Antagonists: Compounds that bind to and block the stimulation of ADENOSINE A1 RECEPTORS.Interleukin 1 Receptor Antagonist Protein: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.Receptor, Adenosine A3: A subtype of ADENOSINE RECEPTOR that is found expressed in a variety of locations including the BRAIN and endocrine tissues. The receptor is generally considered to be coupled to the GI, INHIBITORY G-PROTEIN which causes down regulation of CYCLIC AMP.Receptor, Adenosine A2B: A subclass of adenosine A2 receptors found in the CECUM, the COLON, the BLADDER, and a variety of other tissues. It is generally considered to be a low affinity receptor for ADENOSINE that couples to the GS, STIMULATORY G-PROTEIN.Neurokinin-1 Receptor Antagonists: Compounds that inhibit or block the activity of NEUROKININ-1 RECEPTORS.Receptors, Adenosine A2: A subclass of ADENOSINE RECEPTORS that are generally considered to be coupled to the GS, STIMULATORY G-PROTEIN which causes up regulation of CYCLIC AMP.Adenosine Kinase: An enzyme that catalyzes the formation of ADP plus AMP from adenosine plus ATP. It can serve as a salvage mechanism for returning adenosine to nucleic acids. EC 2.7.1.20.Receptors, Purinergic P1: A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).Adenosine A2 Receptor Agonists: Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.Xanthines: Purine bases found in body tissues and fluids and in some plants.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Histamine H2 Antagonists: Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood.Piperidines: A family of hexahydropyridines.Serotonin 5-HT3 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT3 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT3 RECEPTOR AGONISTS.Excitatory Amino Acid Antagonists: Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.Adenosine A3 Receptor Antagonists: Compounds that selectively bind to and block the activation of ADENOSINE A3 RECEPTORS.Dopamine Antagonists: Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.Angiotensin Receptor Antagonists: Agents that antagonize ANGIOTENSIN RECEPTORS. Many drugs in this class specifically target the ANGIOTENSIN TYPE 1 RECEPTOR.Serotonin 5-HT2 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT2 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN 5-HT2 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more specific 5-HT2 receptor subtypes.Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their specific sites.Purinergic P2 Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2 RECEPTORS.Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.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.Adenosine-5'-(N-ethylcarboxamide): A stable adenosine A1 and A2 receptor agonist. Experimentally, it inhibits cAMP and cGMP phosphodiesterase activity.Theophylline: A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system.Histamine H1 Antagonists: Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood.Receptors, Endothelin: Cell surface proteins that bind ENDOTHELINS with high affinity and trigger intracellular changes which influence the behavior of cells.Receptors, Purinergic: Cell surface proteins that bind PURINES with high affinity and trigger intracellular changes which influence the behavior of cells. The best characterized classes of purinergic receptors in mammals are the P1 receptors, which prefer ADENOSINE, and the P2 receptors, which prefer ATP or ADP.Muscarinic Antagonists: Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Serotonin Antagonists: Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.Leukotriene Antagonists: A class of drugs designed to prevent leukotriene synthesis or activity by blocking binding at the receptor level.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Receptor, Endothelin A: A subtype of endothelin receptor found predominantly in the VASCULAR SMOOTH MUSCLE. It has a high affinity for ENDOTHELIN-1 and ENDOTHELIN-2.Receptors, Serotonin: Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.Receptors, N-Methyl-D-Aspartate: A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.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.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.Dizocilpine Maleate: A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.Serotonin 5-HT1 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT1 RECEPTORS, thereby blocking the actions of SEROTONIN 5-HT1 RECEPTOR AGONISTS. Included under this heading are antagonists for one or more of the specific 5-HT1 receptor subtypes.2-Chloroadenosine: 2-Chloroadenosine. A metabolically stable analog of adenosine which acts as an adenosine receptor agonist. The compound has a potent effect on the peripheral and central nervous system.Biphenyl CompoundsRadioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Adenosine A3 Receptor Agonists: Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.Receptors, Interleukin-1: Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.TetrazolesAdrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.Benzazepines: Compounds with BENZENE fused to AZEPINES.Phenylisopropyladenosine: N-Isopropyl-N-phenyl-adenosine. Antilipemic agent. Synonym: TH 162.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.Nicotinic Antagonists: Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.Purinergic Antagonists: Drugs that bind to and block the activation of PURINERGIC RECEPTORS.Pyrazoles: Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.Pyridines: Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.Adrenergic alpha-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-2 RECEPTORS.Serotonin Receptor Agonists: Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS.Histamine H3 Antagonists: Drugs that selectively bind to but do not activate HISTAMINE H3 RECEPTORS. They have been used to correct SLEEP WAKE DISORDERS and MEMORY DISORDERS.Sulfonamides: A group of compounds that contain the structure SO2NH2.5'-Nucleotidase: A glycoprotein enzyme present in various organs and in many cells. The enzyme catalyzes the hydrolysis of a 5'-ribonucleotide to a ribonucleoside and orthophosphate in the presence of water. It is cation-dependent and exists in a membrane-bound and soluble form. EC 3.1.3.5.Inosine: A purine nucleoside that has hypoxanthine linked by the N9 nitrogen to the C1 carbon of ribose. It is an intermediate in the degradation of purines and purine nucleosides to uric acid and in pathways of purine salvage. It also occurs in the anticodon of certain transfer RNA molecules. (Dorland, 28th ed)Peptides, Cyclic: Peptides whose amino and carboxy ends are linked together with a peptide bond forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS. Some of them are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL).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.Serotonin: 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.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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Purinergic P2X Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2X RECEPTORS. Included under this heading are antagonists for specific P2X receptor subtypes.Azepines: Seven membered heterocyclic rings containing a NITROGEN atom.Losartan: An antagonist of ANGIOTENSIN TYPE 1 RECEPTOR with antihypertensive activity due to the reduced pressor effect of ANGIOTENSIN II.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.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Theobromine: 3,7-Dimethylxanthine. The principle alkaloid in Theobroma cacao (the cacao bean) and other plants. A xanthine alkaloid that is used as a bronchodilator and as a vasodilator. It has a weaker diuretic activity than THEOPHYLLINE and is also a less powerful stimulant of smooth muscle. It has practically no stimulant effect on the central nervous system. It was formerly used as a diuretic and in the treatment of angina pectoris and hypertension. (From Martindale, The Extra Pharmacopoeia, 30th ed, pp1318-9)Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Receptors, Bradykinin: Cell surface receptors that bind BRADYKININ and related KININS with high affinity and trigger intracellular changes which influence the behavior of cells. The identified receptor types (B-1 and B-2, or BK-1 and BK-2) recognize endogenous KALLIDIN; t-kinins; and certain bradykinin fragments as well as bradykinin itself.Endothelin-1: A 21-amino acid peptide produced in a variety of tissues including endothelial and vascular smooth-muscle cells, neurons and astrocytes in the central nervous system, and endometrial cells. It acts as a modulator of vasomotor tone, cell proliferation, and hormone production. (N Eng J Med 1995;333(6):356-63)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.Triazines: Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.Receptors, Neurokinin-1: A class of cell surface receptors for TACHYKININS with a preference for SUBSTANCE P. Neurokinin-1 (NK-1) receptors have been cloned and are members of the G protein coupled receptor superfamily. They are found on many cell types including central and peripheral neurons, smooth muscle cells, acinar cells, endothelial cells, fibroblasts, and immune cells.Receptor, Endothelin B: A subtype of endothelin receptor found predominantly in the KIDNEY. It may play a role in reducing systemic ENDOTHELIN levels.TriazolesNeurons: 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.Behavior, Animal: The observable response an animal makes to any situation.Receptors, Dopamine D2: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.PiperazinesDevazepide: A derivative of benzodiazepine that acts on the cholecystokinin A (CCKA) receptor to antagonize CCK-8's (SINCALIDE) physiological and behavioral effects, such as pancreatic stimulation and inhibition of feeding.Receptors, Cholecystokinin: Cell surface proteins that bind cholecystokinin (CCK) with high affinity and trigger intracellular changes influencing the behavior of cells. Cholecystokinin receptors are activated by GASTRIN as well as by CCK-4; CCK-8; and CCK-33. Activation of these receptors evokes secretion of AMYLASE by pancreatic acinar cells, acid and PEPSIN by stomach mucosal cells, and contraction of the PYLORUS and GALLBLADDER. The role of the widespread CCK receptors in the central nervous system is not well understood.PyrrolidinesReceptors, Vasopressin: Specific molecular sites or proteins on or in cells to which VASOPRESSINS bind or interact in order to modify the function of the cells. Two types of vasopressin receptor exist, the V1 receptor in the vascular smooth muscle and the V2 receptor in the kidneys. The V1 receptor can be subdivided into V1a and V1b (formerly V3) receptors.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.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.Quinoxalines2-Amino-5-phosphonovalerate: The D-enantiomer is a potent and specific antagonist of NMDA glutamate receptors (RECEPTORS, N-METHYL-D-ASPARTATE). The L form is inactive at NMDA receptors but may affect the AP4 (2-amino-4-phosphonobutyrate; APB) excitatory amino acid receptors.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.Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.Receptor, Cannabinoid, CB1: A subclass of cannabinoid receptor found primarily on central and peripheral NEURONS where it may play a role modulating NEUROTRANSMITTER release.Serotonin 5-HT4 Receptor Antagonists: Drugs that bind to but do not activate SEROTONIN 5-HT4 RECEPTORS, thereby blocking the actions of SEROTONIN or SEROTONIN RECEPTOR AGONISTS.Adrenergic Antagonists: Drugs that bind to but do not activate ADRENERGIC RECEPTORS. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters EPINEPHRINE and NOREPINEPHRINE.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.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Receptors, Thromboxane: Cell surface proteins that bind THROMBOXANES with high affinity and trigger intracellular changes influencing the behavior of cells. Some thromboxane receptors act via the inositol phosphate and diacylglycerol second messenger systems.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Injections, Intraventricular: Injections into the cerebral ventricles.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.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Receptors, Neurokinin-2: A class of cell surface receptors for tachykinins that prefers neurokinin A; (NKA, substance K, neurokinin alpha, neuromedin L), neuropeptide K; (NPK); or neuropeptide gamma over other tachykinins. Neurokinin-2 (NK-2) receptors have been cloned and are similar to other G-protein coupled receptors.Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors.Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion.Cannabinoid Receptor Antagonists: Compounds that inhibit or block the activity of CANNABINOID RECEPTORS.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.QuinuclidinesAdrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Receptors, Purinergic P2: A class of cell surface receptors for PURINES that prefer ATP or ADP over ADENOSINE. P2 purinergic receptors are widespread in the periphery and in the central and peripheral nervous system.BenzodiazepinonesKinetics: The rate dynamics in chemical or physical systems.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.Electric Stimulation: Use of electric potential or currents to elicit biological responses.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.Receptors, Histamine H3: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H3 receptors were first recognized as inhibitory autoreceptors on histamine-containing nerve terminals and have since been shown to regulate the release of several neurotransmitters in the central and peripheral nervous systems. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Adenine NucleotidesMineralocorticoid Receptor Antagonists: Drugs that bind to and block the activation of MINERALOCORTICOID RECEPTORS by MINERALOCORTICOIDS such as ALDOSTERONE.QuinolinesDogs: 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)Pyrilamine: A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.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.Capsaicin: An alkylamide found in CAPSICUM that acts at TRPV CATION CHANNELS.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.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.Receptor, Bradykinin B2: A constitutively expressed subtype of bradykinin receptor that may play a role in the acute phase of the inflammatory and pain response. It has high specificity for intact forms of BRADYKININ and KALLIDIN. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.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.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.N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).Vasodilator Agents: Drugs used to cause dilation of the blood vessels.Endothelins: 21-Amino-acid peptides produced by vascular endothelial cells and functioning as potent vasoconstrictors. The endothelin family consists of three members, ENDOTHELIN-1; ENDOTHELIN-2; and ENDOTHELIN-3. All three peptides contain 21 amino acids, but vary in amino acid composition. The three peptides produce vasoconstrictor and pressor responses in various parts of the body. However, the quantitative profiles of the pharmacological activities are considerably different among the three isopeptides.Receptors, Dopamine D1: A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.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).Mice, Inbred C57BLPhenylpropionatesAntihypertensive Agents: Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.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.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Oligopeptides: Peptides composed of between two and twelve amino acids.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)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.Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Receptors, Calcitonin Gene-Related Peptide: Cell surface proteins that bind CALCITONIN GENE-RELATED PEPTIDE with high affinity and trigger intracellular changes which influence the behavior of cells. CGRP receptors are present in both the CENTRAL NERVOUS SYSTEM and the periphery. They are formed via the heterodimerization of the CALCITONIN RECEPTOR-LIKE PROTEIN and RECEPTOR ACTIVITY-MODIFYING PROTEIN 1.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.Isoindoles: Benzopyrroles with the nitrogen at the number two carbon, in contrast to INDOLES which have the nitrogen adjacent to the six-membered ring.Receptors, Corticotropin-Releasing Hormone: Cell surface proteins that bind corticotropin-releasing hormone with high affinity and trigger intracellular changes which influence the behavior of cells. The corticotropin releasing-hormone receptors on anterior pituitary cells mediate the stimulation of corticotropin release by hypothalamic corticotropin releasing factor. The physiological consequence of activating corticotropin-releasing hormone receptors on central neurons is not well understood.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.Receptor, Angiotensin, Type 1: An angiotensin receptor subtype that is expressed at high levels in a variety of adult tissues including the CARDIOVASCULAR SYSTEM, the KIDNEY, the ENDOCRINE SYSTEM and the NERVOUS SYSTEM. Activation of the type 1 angiotensin receptor causes VASOCONSTRICTION and sodium retention.Analgesics: Compounds capable of relieving pain without the loss of CONSCIOUSNESS.Receptors, Tachykinin: Cell surface proteins that bind TACHYKININS with high affinity and trigger intracellular changes influencing the behavior of cells. Three classes of tachykinin receptors have been characterized, the NK-1; NK-2; and NK-3; which prefer, respectively, SUBSTANCE P; NEUROKININ A; and NEUROKININ B.Motor Activity: The physical activity of a human or an animal as a behavioral phenomenon.Receptors, G-Protein-Coupled: The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.Receptors, Angiotensin: Cell surface proteins that bind ANGIOTENSINS and trigger intracellular changes influencing the behavior of cells.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include ADENINE and GUANINE, constituents of nucleic acids, as well as many alkaloids such as CAFFEINE and THEOPHYLLINE. Uric acid is the metabolic end product of purine metabolism.Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752)Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.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.Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.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.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.Vasodilation: The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE.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.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.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.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.Proglumide: A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers.Dioxanes: 1,4-Diethylene dioxides. Industrial solvents. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), dioxane itself may "reasonably be anticipated to be a carcinogen." (Merck Index, 11th ed)Receptor, Serotonin, 5-HT2A: A serotonin receptor subtype found widely distributed in peripheral tissues where it mediates the contractile responses of variety of tissues that contain SMOOTH MUSCLE. Selective 5-HT2A receptor antagonists include KETANSERIN. The 5-HT2A subtype is also located in BASAL GANGLIA and CEREBRAL CORTEX of the BRAIN where it mediates the effects of HALLUCINOGENS such as LSD.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Memantine: AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Receptors, Histamine H2: A class of histamine receptors discriminated by their pharmacology and mode of action. Histamine H2 receptors act via G-proteins to stimulate ADENYLYL CYCLASES. Among the many responses mediated by these receptors are gastric acid secretion, smooth muscle relaxation, inotropic and chronotropic effects on heart muscle, and inhibition of lymphocyte function. (From Biochem Soc Trans 1992 Feb;20(1):122-5)Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.Nucleoside Deaminases: Catalyze the hydrolysis of nucleosides with the elimination of ammonia.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Purinergic P2Y Receptor Antagonists: Compounds that bind to and block the stimulation of PURINERGIC P2Y RECEPTORS. Included under this heading are antagonists for specific P2Y receptor subtypes.

Contribution of adenosine to the depression of sympathetically evoked vasoconstriction induced by systemic hypoxia in the rat. (1/257)

Previous studies have shown that systemic hypoxia evokes vasodilatation in skeletal muscle that is mediated mainly by adenosine acting on A1 receptors, and that the vasoconstrictor effects of sympathetic nerve activity are depressed during hypoxia. The aim of the present study was to investigate the role of adenosine in this depression. In anaesthetised rats, increases in femoral vascular resistance (FVR) evoked by stimulation of the lumbar sympathetic chain with bursts of impulses at 40 or 20 Hz were greater than those evoked by continuous stimulation at 2 Hz with the same number of impulses (120) over 1 min. All of these responses were substantially reduced by infusion of adenosine or by graded systemic hypoxia (breathing 12, 10 or 8 % O2), increases in FVR evoked by continuous stimulation at 2 Hz being most vulnerable. Blockade of A1 receptors ameliorated the depression caused by adenosine infusion of the increase in FVR evoked by 2 Hz only and did not ameliorate the depression caused by 8 % O2 of increases in FVR evoked by any pattern of sympathetic stimulation. A2A receptor blockade accentuated hypoxia-induced depression of the increase in FVR evoked by burst stimulation at 40 Hz, but had no other effect. Neither A1 nor A2A receptor blockade affected the depression caused by hypoxia (8 % O2) of the FVR increase evoked by noradrenaline infusion. These results indicate that endogenously released adenosine is not responsible for the depression of sympathetically evoked muscle vasoconstriction caused by systemic hypoxia; adenosine may exert a presynaptic facilitatory influence on the vasoconstrictor responses evoked by bursts at high frequency.  (+info)

Neuroprotection by caffeine and adenosine A2A receptor blockade of beta-amyloid neurotoxicity. (2/257)

Adenosine is a neuromodulator in the nervous system and it has recently been observed that pharmacological blockade or gene disruption of adenosine A(2A) receptors confers neuroprotection under different neurotoxic situations in the brain. We now observed that coapplication of either caffeine (1-25 micro M) or the selective A(2A) receptor antagonist, 4-(2-[7-amino-2(2-furyl)(1,2,4)triazolo (2,3-a)(1,3,5)triazin-5-ylamino]ethyl)phenol (ZM 241385, 50 nM), but not the A receptor antagonist, 8-cyclopentyltheophylline (200 nM), prevented the neuronal cell death caused by exposure of rat cultured cerebellar granule neurons to fragment 25-35 of beta-amyloid protein (25 micro M for 48 h), that by itself caused a near three-fold increase of propidium iodide-labeled cells. This constitutes the first in vitro evidence to suggest that adenosine A(2A) receptors may be the molecular target responsible for the observed beneficial effects of caffeine consumption in the development of Alzheimer's disease.  (+info)

Synergistic effect of SCH 58261, an adenosine A2A receptor antagonist, and L-DOPA on the reserpine-induced muscle rigidity in rats. (3/257)

The aim of the present study was to find out whether a blockade of adenosine A2A receptors by the selective antagonist, SCH 58261, potentiates the attenuating effect of L-DOPA, the well-known antiparkinsonian drug, on parkinsonian-like muscle rigidity in rats. Muscle tone was examined using a combined mechano- and electromyographic method, which simultaneously measured muscle resistance of a rat hindfoot to passive extension and flexion in the ankle joint and the electromyographic (EMG) activity of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was produced by reserpine (5 mg/kg ip) injected in combination with alpha-methyl-p-tyrosine (alpha-MT, 250 mg/kg ip). L-DOPA (25 mg/kg ip) or SCH 58261 (0.1 mg/kg ip) administered separately, slightly influenced the reserpine + alpha-MT-induced muscle rigidity. However, only ankle joint extension was affected significantly while the effect on flexion of the rat hindfoot was not significant. Neither L-DOPA nor SCH 58261 given separately modified the reserpine-enhanced tonic or reflex EMG activities in both muscles examined. However, when L-DOPA (25 mg/kg) was given together with SCH 58261 (0.1 mg/kg), a clear synergistic effect was seen on both examined movements and muscles. The present results show that the blockade of adenosine A2A receptors potentiates the antiparkinsonian effect of L-DOPA. Since such an effect was seen in different animal models of Parkinson's disease (PD), it seems that co-administration of SCH 58261 may allow for the lowering of the doses of L-DOPA in clinical practice, which indicates a potential therapeutic value of this compound in the treatment of PD.  (+info)

Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. (4/257)

1. Ischemic preconditioning in the brain consists of reducing the sensitivity of neuronal tissue to further, more severe, ischemic insults. We recorded field epsps (fepsps) extracellularly from hippocampal slices to develop a model of in vitro ischemic preconditioning and to evaluate the role of A1, A2A and A3 adenosine receptors in this phenomenon. 2. The application of an ischemic insult, obtained by glucose and oxygen deprivation for 7 min, produced an irreversible depression of synaptic transmission. Ischemic preconditioning was induced by four ischemic insults (2 min each) separated by 13 min of normoxic conditions. After 30 min, an ischemic insult of 7 min was applied. This protocol substantially protected the tissue from the irreversible depression of synaptic activity. 3. The selective adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nm), completely prevented the protective effect of preconditioning. The selective adenosine A2A receptor antagonist 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phe nol (ZM 241385, 100 nm) did not modify the magnitude of fepsp recovery compared to control slices. The selective A3 adenosine receptor antagonists, 3-propyl-6-ethyl-5[ethyl(thio)carbonyl]-2-phenyl-4-propyl-3-pyridinecarboxylate (MRS 1523, 100 nm) significantly improved the recovery of fepsps after 7 min of ischemia. 4. Our results show that in vitro ischemic preconditioning allows CA1 hippocampal neurons to become resistant to prolonged exposure to ischemia. Adenosine, by stimulating A1 receptors, plays a crucial role in eliciting the cell mechanisms underlying preconditioning; A2A receptors are not involved in this phenomenon, whereas A3 receptor activation is harmful to ischemic preconditioning.  (+info)

Adenosine-induced IL-6 expression in pituitary folliculostellate cells is mediated via A2b adenosine receptors coupled to PKC and p38 MAPK. (5/257)

Activation of adenosine receptors in folliculostellate (FS) cells of the pituitary gland leads to the secretion of IL-6 and vascular endothelial growth factor (VEGF). We investigated the action of adenosine A2 receptor agonists on IL-6 and VEGF secretion in two murine FS cell lines (TtT/GF and Tpit/F1), and demonstrated a rank order of potency, 5'-N-ethylcarboxamidoadenosine (NECA)>2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine>adenosin e, suggesting mediation via the A2b receptor. NECA-mediated IL-6 release was inhibited by the PLC inhibitor 1-[6-((17beta-3-methoxyestra-1,3,5(10)-tiene-17-yl)amino)hexyl]-1H-pyrrole-2,5-di one, the PI3 kinase inhibitor wortmannin and the PKC inhibitors bisindolylmaleimide 1 and bisindolymaleimide X1 HCl (Ro-32-0432). NECA-mediated IL-6 release was attenuated (<50%) by the extracellular signal-regulated kinase MAPK inhibitor 2'-amino-3'-methoxyflavone, and completely (>95%) inhibited by the p38 MAPK inhibitor 4-(4-fluorophenyl)-2-(4-methylsulphinylphenyl)-5-(4-pyridyl)1H-imidazole. NECA stimulates p38 MAPK phosphorylation that is inhibited by Ro-32-0432 but not by wortmannin. Dexamethasone inhibits NECA-stimulated IL-6 and VEGF secretion. These findings indicate that adenosine can stimulate IL-6 secretion in FS cells via the A2b receptor coupled principally to PLC/PKC and p38 MAPK; such an action may be important in the modulation of inflammatory response processes in the pituitary gland.  (+info)

Possible targeting of G protein coupled receptors to manipulate inflammation in vivo using synthetic and natural ligands. (6/257)

Cyclic AMP elevating Gs protein coupled receptors were considered for a long time to be immunosuppressive. One of these receptors, adenosine A(2A) receptor, was implicated in a physiological mechanism that down regulates inflammation and protects tissues from excessive immune mediated damage. Targeting of these receptors by selective agonists may lead to better protocols of anti-inflammatory treatments. At the same time inhibiting the Gs protein coupled mediated signalling with antagonists could be explored in studies of approaches to enhance inflammation and tissue damage. Enhancement of targeted tissue damage is highly desirable when it is cancerous tissue, while enhancement of inflammatory events might be desirable in the development of new vaccine adjuvants.  (+info)

Involvement of adenosine A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of cocaine and methamphetamine in rats. (7/257)

Adenosine, by acting on adenosine A1 and A2A receptors, is known to antagonistically modulate dopaminergic neurotransmission. We have recently reported that nonselective adenosine receptor antagonists (caffeine and 3,7-dimethyl-1-propargylxanthine) can partially substitute for the discriminative-stimulus effects of methamphetamine. In the present study, by using more selective compounds, we investigated the involvement of A1 and A2A receptors in the adenosinergic modulation of the discriminative-stimulus effects of both cocaine and methamphetamine. The effects of the A1 receptor agonist N6-cyclopentyladenosine (CPA; 0.01-0.1 mg/kg) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT; 1.3-23.7 mg/kg) and the A2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS 21680; 0.03-0.18 mg/kg) and antagonist 3-(3-hydroxypropyl)-8-(3-methoxystyryl)-7-methyl-1-propargylxanthin phosphate disodium salt (MSX-3; 1-56 mg/kg) were evaluated in rats trained to discriminate either 1 mg/kg methamphetamine or 10 mg/kg cocaine from saline under a fixed-ratio 10 schedule of food presentation. The A1 and A2A receptor antagonists (CPT and MSX-3) both produced high levels of drug-lever selection when substituted for either methamphetamine or cocaine and significantly shifted dose-response curves of both psychostimulants to the left. Unexpectedly, the A2A receptor agonist CGS 21680 also produced drug-appropriate responding (although at lower levels) when substituted for the cocaine-training stimulus, and both CGS 21680 and the A1 receptor agonist CPA significantly shifted the cocaine dose-response curve to the left. In contrast, both agonists did not produce significant levels of drug-lever selection when substituted for the methamphetamine-training stimulus and failed to shift the methamphetamine dose-response curve. Therefore, adenosine A1 and A2A receptors appear to play important but differential roles in the modulation of the discriminative-stimulus effects of methamphetamine and cocaine.  (+info)

Antinociceptive effects of novel A2B adenosine receptor antagonists. (8/257)

Caffeine, an adenosine A1, A2A, and A2B receptor antagonist, is frequently used as an adjuvant analgesic in combination with nonsteroidal anti-inflammatory drugs or opioids. In this study, we have examined the effects of novel specific adenosine receptor antagonists in an acute animal model of nociception. Several A2B-selective compounds showed antinociceptive effects in the hot-plate test. In contrast, A1- and A2A-selective compounds did not alter pain thresholds, and an A3 adenosine receptor antagonist produced thermal hyperalgesia. Evaluation of psychostimulant effects of these compounds in the open field showed only small effects of some antagonists at high doses. Coadministration of low, subeffective doses of A2B-selective antagonists with a low dose of morphine enhanced the efficacy of morphine. Our results indicate that analgesic effects of caffeine are mediated, at least in part, by A2B adenosine receptors.  (+info)

*Adenosine A2A receptor

... a potent and selective adenosine A2 receptor antagonist". European Journal of Pharmacology. 267 (3): 335-41. doi:10.1016/0922- ... Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused ... As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. The adenosine A2A receptor has also been ... "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ...

*Adenosine A3 receptor

... a novel specific adenosine A(3) receptor antagonist with adenosine A(3) receptor agonists both in vitro and in vivo". Eur. J. ... 1997). "Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 ... a novel ligand that demonstrates both adenosine A(2A) receptor agonist and adenosine A(3) receptor antagonist activity". ... is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors ...

*CGS-15943

"Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, ... CGS-15943 is a drug which acts as a potent and reasonably selective antagonist for the adenosine receptors A1 and A2A, having a ... It was one of the first adenosine receptor antagonists discovered that is not a xanthine derivative, instead being a ... Holtzman SG (1991). "CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and ...

*Diprophylline

Schwabe, U; Ukena, D; Lohse, MJ (September 1985). "Xanthine Derivatives as Antagonists at A1 and A2 Adenosine Receptors". ... It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor. Xanthine "International Non-Proprietary Names. ...

*Cartazolate

... activity as antagonists of A1- and A2-adenosine receptors". Biochemical Pharmacology. 37 (4): 655-64. doi:10.1016/0006-2952(88) ... It is also known to act as an adenosine antagonist at the A1 and A2 subtypes and as a phosphodiesterase inhibitor. Cartazolate ... "Perturbation of benzodiazepine receptor binding by pyrazolopyridines involves picrotoxinin/barbiturate receptor sites". Journal ... O'Brien, Robert (1986). Receptor binding in drug research. New York: Dekker. p. 519. ISBN 0-8247-7548-1. US Patent 3966746 ...

*Theophylline

... and reduces inflammation and innate immunity nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors ... Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Prog Clin Biol ... asthma infant apnea Blocks the action of adenosine; an inhibitory neurotransmitter that induces sleep, contracts the smooth ...

*Adenosine A1 receptor

... an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal ... Caffeine may reduce cerebral blood flow in premature infants, it is presumed by blocking vascular A2 ARs. Thus, it may prove ... The adenosine A1 receptor is one member of the adenosine receptor group of G protein-coupled receptors with adenosine as ... The adenosine A1 receptor has been found to be ubiquitous throughout the entire body. Activation of the adenosine A1 receptor ...

*DMPX

... is a caffeine analog which displays affinity to A2 adenosine receptors, in contrast to the A1 subtype receptors. DMPX had 28× ... a potent and selective in vivo antagonist of adenosine analogs. Life Sci. 1988;43(21):1671-84. PMID 3193854. ...

*Thromboregulation

These signaling elements include thromboxane A2, receptor type α, phospholipase Cβ3, and IP3 receptors. Signalization in ... It belongs to the homologous family of glycoprotein IIb-IIa antagonists. Kistrin has an adhesion site that binds to GP IIb-IIIa ... cAMP, cyclic adenosine monophosphate, phosphorylate messengers via protein kinase A (PKA). ... TX2 effects are mediated by G protein-coupled receptors, subtypes TPα and TPβ. Both receptors mediate phospholipase C ...

*Etazolate

It acts as a positive allosteric modulator of the GABAA receptor at the barbiturate binding site, as an adenosine antagonist of ... the A1 and A2 subtypes, and as a phosphodiesterase inhibitor selective for the PDE4 isoform. It is currently in clinical trials ... ISBN 3-7643-1837-6. Williams M, Jarvis MF (February 1988). "Adenosine antagonists as potential therapeutic agents". ... Zezula J, Slany A, Sieghart W (April 1996). "Interaction of allosteric ligands with GABAA receptors containing one, two, or ...

*Prostaglandin DP1 receptor

Asapiprant (S-555739) and Laropiprant are selective receptor antagonists of DP1 whereas Vidupiprant is a receptor antagonist ... the DP1-dependent stimulation of adenosine formation and subsequent simulation of the Adenosine A2A receptor by adenosine. In ... thromboxane A2, with PGD2 being more than 100-fold more potent than PGE2 in binding to and stimulating DP1. (http://www. ... Prostaglandin receptors Prostanoid receptors Prostaglandin DP2 receptor Eicosanoid receptor GRCh38: Ensembl release 89: ...

*GPCR oligomer

"Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes ... "Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists". Science. 330 (6007): 1066-71. doi: ... In 1991, the phenomenon of receptor crosstalk was observed between adenosine A2A (A2A) and dopamine D2 receptor (DRD2) thus ... two adenosine A2A receptors and two dopamine D2 receptors). Maggio and co-workers showed in 1993 the ability of the muscarinic ...

*Nociceptin receptor

"Modification of nociception and morphine tolerance by the selective opiate receptor-like orphan receptor antagonist (-)-cis-1- ... Fukuda K, Shoda T, Morikawa H, Kato S, Mima H, Mori K (1998). "Activation of phospholipase A2 by the nociceptin receptor ... causing an intracellular decrease in cyclic adenosine monophosphate(cAMP) levels, an important second messenger for many signal ... receptor or kappa-type 3 opioid receptor, is a protein that in humans is encoded by the OPRL1 (opioid receptor-like 1) gene. ...

*Multiple electrode aggregometry

The GPIIb/IIIa antagonist blocks the binding of fibrinogen to the GPIIb/IIIa receptors, preventing the formation of platelet- ... Adenosine diphosphate (ADP) is a platelet agonist. When it is added to saline-diluted whole blood in the test cuvette, it ... and PGH2 is then converted to thromboxane A2 (TXA2) by thromboxane synthase. TXA2 increases platelet aggregation, promotes ... Thrombin receptor activating peptide-6 (TRAP-6) activates platelets through the thrombin receptor protease activated receptor-1 ...

*5-HT1D receptor

"Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics. 11 (1 ... mixed 5-HT1B/1D antagonist) LY-310,762 LY-367,642 LY-456,219 LY-456,220 5-HT1 receptor 5-HT receptor GRCh38: Ensembl release 89 ... 5-hydroxytryptamine (serotonin) receptor 1D, also known as HTR1D, is a 5-HT receptor, but also denotes the human gene encoding ... 5HT1D receptor is a G protein linked receptor that activates an intracellular messenger cascade to produce an inhibitory ...

*Adenosine

The A1 receptors couple to Gi/o and decreases cAMP levels, while the A2 adenosine receptors couple to Gs, which stimulates ... This is being contended and it is now considered a relative contraindication (however, selective adenosine antagonists are ... In the US, Adenosine is marketed as Adenocard. In India Adenosine is sold as Adenoscan (Cipla) All adenosine receptor subtypes ... Adenosine is believed to be an anti-inflammatory agent at the A2A receptor. Topical treatment of adenosine to foot wounds in ...

*PRKCE

Yang Z, Sun W, Hu K (Apr 2012). "Molecular mechanism underlying adenosine receptor-mediated mitochondrial targeting of protein ... Perjés Á, Skoumal R, Tenhunen O, Kónyi A, Simon M, Horváth IG, Kerkelä R, Ruskoaho H, Szokodi I (2014). "Apelin increases ... Gray MO, Karliner JS, Mochly-Rosen D (Dec 1997). "A selective epsilon-protein kinase C antagonist inhibits protection of ... Yang Z, Sun W, Hu K (Apr 2012). "Molecular mechanism underlying adenosine receptor-mediated mitochondrial targeting of protein ...

*Proton-pump inhibitor

... called H2-receptor antagonists. PPIs are among the most widely sold drugs in the world, and the first one, omeprazole, is on ... Lucendo AJ, Arias Á, Molina-Infante J (2015). "Efficacy of Proton Pump Inhibitor Drugs for Inducing Clinical and Histological ... Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ... H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux ...

*Molecular and epigenetic mechanisms of alcoholism

... glutamate receptor antagonist on ethanol consumption by genetic drinking rats. Alcohol, 40, 494-497. Hodge, C.W., Miles, M.F., ... Katsura, M., Shibasaki, M., Hayashida, S., Torigoe, F., Tsujimura, A., Ohkuma, S. (2006) Increase in expression of a1 and a2/d1 ... Pandey, S.C., Roy, A., Zhang, H. (2003). The decreased phosphorylation of cyclic adenosine monophosphate (cAMP) response ... receptors are glutamate receptors particularly important in long-term potentiation in neurons. These receptors have been linked ...

*Arachidonate 5-lipoxygenase

Montelukast, Zafirlukast, and Pranlukast are receptor antagonists for the Cysteinyl leukotriene receptor 1 which contributes to ... The cytosolic PLA2 set (i.e. cPLA2s) of PLA2 enzymes (cPLA2; see Phospholipase A2#Cytosolic phospholipases A2) in particular ... may serve as a mobile lid over ALOX5's substrate-binding site An Adenosine triphosphate (ATP) binding site; ATP is crucial for ... as well as of LTC4 and LTD4 receptor antagonists have proven inferior to corticosteroids as single drug therapy for persistent ...

*12-Hydroxyheptadecatrienoic acid

... trienoic acid as a thromboxane A2 receptor antagonist with minimal intrinsic activity". British Journal of Haematology. 101 (1 ... to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine ... BLT1 receptor) and its low affinity BLT2 receptor (Kd=23 nM); both receptors are G protein coupled receptors that, when ligand- ... Hicks, A; Monkarsh, S. P.; Hoffman, A. F.; Goodnow Jr, R (2007). "Leukotriene B4 receptor antagonists as therapeutics for ...

*Neurotransmitter

... direct-acting Antagonist and indirect-acting Antagonists: Direct-acting antagonist- which takes up space present on receptors ... Rinaman L (February 2011). "Hindbrain noradrenergic A2 neurons: diverse roles in autonomic, endocrine, cognitive, and ... Peptides: somatostatin, substance P, cocaine and amphetamine regulated transcript, opioid peptides Purines: adenosine ... An irreversible antagonist binds so strongly to the receptor as to render the receptor unavailable for binding to the agonist. ...

*MicroRNA

Most commonly, enzymes known as adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine (A to I) transitions. ... The specific microRNA, miR-506 has been found to work as a tumor antagonist in several studies. In a 2014 study, a significant ... miR-382 is the target for the dopamine receptor D1 (DRD1), and its overexpression results in the upregulation of DRD1 and delta ... December 2003). "High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ...

*List of OMIM disorder codes

IGF1R Interleukin 1 receptor antagonist deficiency; 612852; IL1RN Interleukin-2 receptor, alpha chain, deficiency of; 606367; ... IHH Brachydactyly type A2; 112600; BMPR1B Brachydactyly type A2; 112600; GDF5 Brachydactyly type B1; 113000; ROR2 Brachydactyly ... APC Adenosine deaminase deficiency, partial; 102700; ADA Adenosine triphosphate, elevated, of erythrocytes; 102900; PKLR ... associated with acetylcholine receptor deficiency; 608931; MUSK Myasthenic syndrome, congenital, associated with acetylcholine ...
The IUPHAR/BPS Guide to Pharmacology. istradefylline ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.
In 6-OHDA-lesioned rats, repeated administration produces behavioral sensitization, manifested as a marked increase in l-Dopa-induced contralateral rotations across days of treatment (Henry et al., 1998). Behavioral sensitization has been suggested to predict the development of dyskinesias after chronic treatment with l-Dopa (Tronci et al., 2007). Here, we found that l-Dopa produced behavioral sensitization after only 4 days of treatment in 6-OHDA-lesioned rats. However, when l-Dopa was delivered concurrently with preladenant, the rats displayed no behavioral sensitization for as long as 23 days of treatment. The blockade of behavioral sensitization by preladenant in this model suggests that this agent may not only have antiparkinsonian effects on its own but also may reduce dyskinesias when used in combination with l-Dopa.. Aside from the motor symptoms that characterize PD, there are a collection of nonmotor symptoms that are not treated by current pharmacotherapies. One of the most severe is ...
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies. ...
UPDRS is a clinician based rating scale used to measure motor impairments and disability; it assesses 6 features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the participant. UPDRS Part 2 is Activities of Daily Living score and ranges from 0-52. UPDRS Part 3 is Motor Examination and ranges from 0-108. The combined scores of Parts 2 and 3 can range from 0-160 with the higher score indicating the worse condition. A Responder is defined as a participant with at least 20% improvement in UPDRS2+3 from Baseline to Week 26 (End of Part 1 Treatment); a participant with at least a 20% decrease from Baseline score in UPDRS2+3 is defined as a responder. The proportion of Responders was analyzed using a generalized linear mixed model with treatment effect, strata and Baseline UPDRS2+3 as a covariate, and treatment-by-time interaction as fixed effects and subject as random effect ...
Discouraging news this week for the Parkinson s community, as drug giant Merck announced that they will discontinue their program developing a novel therapy for PD called preladenant.
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Disclosed are processes for the synthesis of novel compounds that are A.sub.2B adenosine receptor antagonists, having the structure of Formula I or Formula II: ##STR00001## by cyclizing a compound of the formula (3): ##STR00002##
SCH 442416 is a selective adenosine A2A receptor antagonist; binds to human and rat A2A receptors with high affinity (Ki values are 0.048 and 0.5 nM respectively). Displays > 23000-fold selectivity for hA2A over hA1 in vitro with minimal affinity for h
DESCRIPTION: (Adapted from the Investigators Abstract): Adenosine administered as an aerosol to asthmatics causes bronchoconstriction, while in non-asthmatics adenosine causes bronchodilation. This occurs because the activation of A2B adenosine receptors on sensitized mast cells triggers degranulation, releasing histamine, leukotrienes, and other allergic mediators. A2B adenosine receptors are blocked by theophylline, a xanthine that is effective in treating asthma. However, theophylline is a non-selective antagonist of all four adenosine receptor subtypes and produces side effects due primarily to A1 receptor blockade, including insomnia and diuresis. The incidence of asthma is increasing and current treatment options are limited. New drugs that are potent and selective antagonists of A2B adenosine receptors have great potential for the treatment of asthma and other allergic diseases. Adenosine Therapeutics, LLC owns the first potent and selective A2B antagonists. The purpose of this phase I ...
ALI is one of the leading causes of morbidity and mortality of critical illness with extremely limited therapeutic options. In the present study, we pursued the hypothesis that tissue-specific adenosine signaling events through the A2B adenosine receptor contribute to lung protection and can thus be targeted for ALI treatment. To make progress on this front, we performed a head-to-head comparison of mice with genetic deletion of Adora2b in the myeloid lineage, vascular endothelial cells, or alveolar epithelial cells. Interestingly, we only observed a phenotype in mice with tissue-specific Adora2b deletion in alveolar epithelial cells, closely resembling the observed detrimental effects of global Adora2b deletion during ALI. Interestingly, the injurious effects of our two-hit model where an inflammatory event (i.t. LPS treatment) is followed by injurious mechanical ventilation seem to be supra-additive compared with the effects of injurious ventilation or LPS i.t. alone. Based on these findings ...
The A2b adenosine receptor (A2bAR) is a G-protein coupled receptor that, upon binding of adenosine, activates adenylyl cyclase and mediates downstream effects through secondary messengers, including cyclic 35 AMP (cAMP) and Ca++. We have previously demonstrated that A2bAR knockout (KO) KO mice, post-high fat diet (HFD) develop a type 2 diabetic (T2D) phenotype, evidenced by elevated plasma insulin and glucose. Pancreatic islets from A2bAR KO mice demonstrated insulin hypersecretion post-4 weeks HFD, and high glucose challenge. To further understand the underlying mechanism, we focused on the contribution of the pancreatic A2bAR to this phenomnena. cAMP has been demonstrated to be a significant amplifier of glucose-stimulated insulin secretion. Through the use of A2bAR KO islets and diet-induced stress, we identified a new dual role for cAMP in mediating insulin secretion, dependent on cAMP level and duration. Short exposure to elevated cAMP indeed causes insulin hypersecretion. cAMP has, ...
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chemBlink provides information about CAS # 3945-69-5, 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methyl morpholinium chloride, DMTMM, molecular formula: C10H17ClN4O3.
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A review. The low affinity A2B adenosine receptor, like any other adenosine receptor subtype, belongs to the super-family of seven transmembrane domain G protein-coupled receptors (7TMs GPCR) and is classified by the GPCR database in the family of rhodopsin like receptors (Class A of GPCR). It has been cloned from various species, including rat and human, and its sequences are highly similar across species, ranging from 85% identity between human and mouse and 95% identity between rat and mouse. The A2B receptors show a ubiquitous distribution, the highest levels are present in cecum, colon and bladder, followed by blood vessels, lung, eye and mast cells. Through A2B receptors adenosine seems to cause mast cells degranulation, vasodilation, cardiac fibroblast proliferation, inhibition of Tumor Necrosis Factor (TNF-α), increased synthesis of interleukin-6 (IL-6), stimulation of Cl- secretion in intestinal epithelia and hepatic glucose prodn. Hence, A2B adenosine receptor agonists could be useful ...
Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted for heart rate (2.04 ± 0.34 vs. 2.12 ± 0.27, p = NS), but persisted between regadenoson and dipyridamole (2.04 ± 0.34 vs. 1.77 ± 0.33, p = ...
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This trial will investigate the effects of single doses of preladenant and placebo on the dyskinesia and antiparkinsonian actions of a levodopa infusion.
This study was assessing the Regadenoson administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Alone for Myocardial Perfusion
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This work done by an eminent group in the area raises concerns over the use of regadenoson for clinical stress testing, whether done by PET or SPECT. Invasive and pharmacologic studies had previously demonstrated peak regadenoson effect at approximately 1-2 minutes after injection, consistent with the findings of the present study. Stress labs which are not already following a 1- to 2-minute delay may wish to consider introducing one.. There are several reasons to view these results with caution, however. First, many prior studies had compared regadenoson to other vasodilators using a variety of techniques including PET, SPECT, and invasive methods. In general, no significant differences or only minimal differences, below the level of clinical relevance, were observed. The reasons for the discrepancies are unclear.. One longstanding concern with regards to regadenoson has been the use of a single fixed dose without weight adjustment, as is usually done for other vasodilators. The investigators ...
Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining. Manufactured by Astellas and FDA approved April 10, 2008.
We investigated the electrophysiological effects of cardiac hypertrophy induced by different experimental models. Comparison of the action potentials of hypertrophied and control rat hearts reveals a pronounced prolongation of the action potential fo
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Microwave Induced Synthesis of 3-Aryl-6-(6-/8-substituted 4-chloroquinoline-3-yl) - s -triazolo [3,4-|em|b]|/em| −1,3,4-thiadiazoles | Ren-Zhong Qiao; Xta-Ptag Hui; Peng-Fei Xu; Zi-Yi Zhang; Dong-Liang Cheng | download | BookSC. Download books for free. Find books
1-(5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylamino)-1-deoxy-5-O-phosphono-D-ribitol, 1-(5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-ylamino)-1-deoxy-D-ribitol 5-(dihydrogen phosphate), 1-[(5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-yl)amino]-1-deoxy-5-O-phosphono-D-ribitol ...
Extracellular accumulation of adenosine in response to myocardial ischemia and tissue damage is an important event in the control of many aspects of tissue repair, including revascularization. This study has demonstrated that A2B adenosine receptors can regulate paracrine functions of cardiac mesenchymal stem-like cells involved in regulation of angiogenesis. Our study revealed that cardiac Sca-1+CD31− stromal cells predominantly express mRNA encoding the A2B adenosine receptor subtype and considerably lower levels of A2A adenosine receptor transcripts. Of importance, stimulation of adenosine receptors promoted release of the major proangiogenic factor VEGF from Sca-1+CD31− stromal cells. Stimulation of adenosine receptors on Sca-1+CD31− stromal cells also increased the release of CXCL1 and IL-6, factors known to promote angiogenesis (Strieter et al., 1995; Hernández-Rodríguez et al., 2003). Using conditionally immortalized mouse cardiac Sca-1+CD31− stromal cell lines, we demonstrated ...
Corresponding Author: Anaclet Ngezahayo Department of Cell Physiology and Biophysics, Institute of Cell Biology and Biophysics, Leibniz University Hannover, Herrenhäuser Straße 2, Hannover, 30419 (Germany ...
2,6-Bis(5,6-diisopropyl-1,2,4-triazin-3-yl)pyridine: a highly selective N-donor ligand studied by TRLFS, liquid-liquid extraction and molecular ...
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Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines such as I are prepd. as selective adenosine A2a and A3 receptor antagonists. Pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines substituted at the 9-position retain receptor affinity but lose selectivity for the adenosine A2a and A3 receptors over other adenosine receptors. Replacement of the furan moiety present in the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine with a Ph or a substituted arom. ring abolishes affinity at all the adenosine receptor subtypes, demonstrating that the furanyl ring is a necessary structural element to guarantee interaction with the adenosine receptor surface; replacement of the furan ring with an ortho-ethoxy-substituted arom. ring did not enhance affinity. Introduction of a N-methylpiperazinomethyl or morpholinomethyl function at the 5 position of the furanyl ring of I or introduction of a methylsulfanyl moiety at the 9-position of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines yields inhibitors with improved ...
The low-affinity A2B receptor is known to mediate proinflammatory effects of adenosine by up-regulating production of cytokines and growth factors. This view has been supported by a large body of evidence provided by pharmacological analysis of adenosine-dependent cytokine and growth factor secretion in various cells, tissues, and organs (8, 11, 13, 18, 31, 32, 33, 34, 35, 36, 37, 38). Pharmacological inhibition of A2B receptors significantly reduced elevations in proinflammatory cytokines as well as mediators of airway remodeling induced by high adenosine levels in the lungs of ADA-deficient mice (8). In the ragweed allergic mouse model, A2B antagonism plays an important role in inhibition of airway reactivity and inflammation (39, 40). In agreement with data obtained in these animal models of pulmonary inflammation, stimulation of A2B receptors in the human mast cell line HMC-1 was shown to induce secretion of proinflammatory Th2 cytokines IL-4 and IL-13 (11, 12), as well as angiogenic factors ...
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PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Action adenosinergic funds due to a direct interaction with adenozinovymi (purine) receptors and indirect effect on the disintegration and accumulation of adenosine (one of the purine neuromodulators). Specialized purine receptors (post - and presynaptic), divided into the P1 receptors (highly sensitive to adenosine) and P2 receptors (more sensitive to ATP). Both types are found in the Central nervous system, cardiovascular and respiratory system, lymph and platelets, etc.. It is known that adenosine has mainly cardiovascular effects, manifested by vasodilatation (with improvement of microcirculation and reduction of platelet aggregation) and negative Ino-, Chrono and dromotropony effects on the heart associated with inhibition of intracellular transport of calcium ions. A number of drugs (dipyridamole, papaverine, etc.) affect the metabolism of adenosine, contribute to its accumulation in the myocardium or potentiate the effect; used as koronarolitikov the disease ...
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A new series of 2,6,9-trisubstituted adenines (5-14) have been prepared and evaluated in radioligan d binding studies for their affinity at the human A1, A2A and A3 adenosine receptors and in adenylyl cyclase experiments for their potency at the human A2B subtype. From this preliminary study the conclusion can be drawn that introduction of bulky chains at the N6 position of 9-propyladenine significantly increased binding affinity at the human A1 and A3 adenosine receptors, while the presence of a chlorine atom at the 2 position resulted in a not univocal effect, depending on the receptor subtype and/or on the substituent present in the N6 position. However, in all cases, the presence in the 2 position of a chlorine atom favoured the interaction with the A2A subtype. These results demonstrated that, although the synthesized compounds were found to be quite inactive at the human A2B subtype, adenine is a useful template for further development of simplified adenosine receptor antagonists with ...
In a group of control subjects without history of ischemic heart disease or evidence of significant coronary stenosis on coronary angiography, Lieu et al. (2) compared the effects of the bolus intravenous administration of regadenoson (10 to 500 μg) with that of intracoronary adenosine (18 μg) on coronary flow. They demonstrated a significant variability with regard to peak coronary flow velocity as assessed with an intracoronary Doppler-tipped guidewire following administration of regadenoson ranging from 0.5 to 2.3 min. Regadenoson was also shown to increase peak coronary flow in a dose-dependent manner. These investigators did appropriately withhold all other drugs that could have potentially affected coronary flow, and still produced the observed variability in response to regadenoson stress. These important observations with regard to the variability of the coronary flow response must be taken into consideration when applying regadenoson stress in conjunction with quantitative dynamic ...
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1,2,4]Triazolo[1,5-a]pyridine derivatives are important heterocyclic compounds which exhibit antifungal, anticancer and anti-inflammatory activities (Luo & Hu, 2006; Liu & Hu, 2002). Despite possessing outstanding biological activities, only a few [1,2,4]triazolo[1,5-a]pyridines are known. Some commonly used synthetic methods are the annulation of the 1,2,4-triazole ring starting with amino substituted pyridines by a multistep procedure (Jones & Sliskovic, 1983). Previously, imidazo[1,5-a]pyridines, pyrazolo[1,5-a]pyridines, imidazo[1,2-a]pyridines and indolizines had been synthesized by a novel tandem reaction in our group (Wang et al., 2003; Ge et al., 2009; Jia et al., 2010). As an extension of this work, the synthesis of [1,2,4]triazolo[1,5-a]pyridine heterocycles through this procedure has been undertaken. We present here the crystal structure of one of such compounds, ethyl 8-phenyl-6-methyl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylate.. In title compound (Fig. 1) the the ...
Adenosine mediates many physiological functions via activation of extracellular receptors. The modulation of cell growth by adenosine was found to be receptor-mediated. In A431 cells adenosine evoked a biphasic response in which a low concentration (~10 μM) produced inhibition of colony formation but at higher concentrations (up to 100 μM) this inhibition was progressively reversed. Evidence for the involvement of A1 (inhibitory) and A2 (stimulatory) adenosine receptors in regulating cell growth of these tumor cells was obtained through plating efficiency studies based on the relative potency of adenosine agonists and antagonists. When both A1 and A2 receptors were blocked, colony formation or growth was not inhibited at low concentrations of adenosine but was inhibited at high adenosine concentrations ...
Adenosine analogues which act selectively at adenosine receptors and which act in general as adenosine antagonists are disclosed. From in vitro studies it is known that specific physiological effects can be distinguished as a result of this selectivity and that adenosine receptor activity in vitro correlates with adenosine receptor activity in vivo. Pharmaceutical preparations of the subject compounds can be prepared on the basis of the selective binding activity of the compounds disclosed herein which will enhance certain physiological effects while minimizing others, such as decreasing blood pressure without decreasing heart rate.
Restenosis, characterized by enhanced neointimal lesion development attributable to excessive SMC proliferation, is still a major concern after percutaneous transluminal coronary angioplasty treatment of patients experiencing (acute) cardiovascular syndromes. In search for novel therapeutic treatment modalities, our attention was turned to the A2B adenosine receptor, which has been shown to be involved in the proliferation of vascular SMCs in rats, as well as in humans.14,27,28 In this study, we thus sought to investigate the therapeutic potential of BAY60-6583, an agonist for this receptor subtype. The compound behaved as a selective probe for the (human) adenosine A2B receptor in radioligand-binding studies, although it displayed affinity for the adenosine A1 receptor. In fact, this is the first report that shows a full radioligand-binding analysis over all 4 subtypes of human adenosine receptors. Auchampach et al29 evaluated the compound in radioligand-binding studies on adenosine A2B ...
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A new series of pyrazolotriazolopyrimidines bearing different substitutions on the phenylcarbamoyl moieties at the N5 position, being highly potent and selective human A3 adenosine receptor antagonists, is described. The compds. represent an extension and an improvement of our previous work on this class of compds. (J. Med. Chem. 1999, 42, 4473-4478; J. Med. Chem. 2000, 43, 4768-4780). All the synthesized compds. showed A3 adenosine receptor affinity in the subnanomolar range and high levels of selectivity in radioligand binding assays at the human A1, A2A, A2B, and A3 adenosine receptors. In particular, the effect of the substitution and its position on the Ph ring have been studied. From binding data, it is evident that the unsubstituted derivs. on the Ph ring (e.g., compd. 59, hA3 = 0.16 nM, hA1/hA3 = 3713, hA2A/hA3 = 2381, hA2B/hA3 = 1388) showed the best profile in terms of affinity and selectivity at the human A3 adenosine receptors. The introduction of a sulfonic acid moiety at the para ...
Scientists have found a possible new therapeutic target against atherosclerosis resulting from a diet high in fat and cholesterol.. The researchers from Boston University School of Medicine (BUSM) have identified for the first time the A2b adenosine receptor (A2bAR) as an agent responsible for protection against early stages of atherosclerosis.. Adenosine is a metabolite produced naturally by cells at low levels, and at higher levels during exercise or stress.. Adenosine binds to and activates cell surface receptors, one of which is the A2bAR. Previous studies have described the A2bAR as anti-inflammatory and protective against kidney ischemia, cardiac reperfusion injury and restenosis, typically via bone marrow cell signals.. In mouse models, BUSM researchers found atherosclerosis induced by a high-fat diet was more pronounced in the absence of the A2bAR.. They also found bone marrow transplantation experiments indicated that A2bAR bone marrow cell signals alone were not sufficient to elicit ...
Cyclic 3, 5-[14C]AMP was measured in platelets that had first been incubated with [14C]adenine. Maximum increases of 2-4-fold were observed 0.5 min after addition of 10-40 µM adenosine. Smaller increases were obtained with higher concentrations of adenosine. In 0.5-min incubations 2-chloroadenosine was less effective than adenosine at concentrations below 20 µM and more effective at concentrations above 100 µM. Incorporation of 1-10 µM adenosine into platelets was inhibited at least 96% by p-nitrobenzylthioguanosine without any effect on the increase in cyclic [14C]AMP caused by these concentrations of adenosine, suggesting that adenosine acts at an extracellular site. With higher adenosine concentrations, p-nitrobenzylthioguanosine was less effective in inhibiting incorporation of adenosine but blocked the decline in cyclic [14C]AMP levels observed on increasing the adenosine concentration above 40 µM. This inhibitory effect of high adenosine concentrations on the accumulation of cyclic ...
HIC-Up files for compound 2SA 2-(9-(3,4-dihydroxy-5-phosphonooxymethyl-tetrahydro- furan-2-yl)-9h-purin-6-ylamino)-succinic acid; adenylosuccinic acid tetrahydro-furan-2-yl)-9h-purin-6-ylamino)- succinic acid
4-amino-6-(dibutylamino)-1,3,5-triazin-2-yl hydrosulfide - chemical structural formula, chemical names, chemical properties, synthesis references
Adenosine Sanolabor is a medicine available in a number of countries worldwide. A list of US medications equivalent to Adenosine Sanolabor is available on the Drugs.com website.
Three A3 adenosine receptor (AR) antagonists (1-3) selected from 4-acylamino-6-alkyloxy-2-alkylthiopyrimidines previously investigated by us were modified by inserting a methyl group on their ether or thioether side chains. These compounds gave us the chance to evaluate whether their higher lipophilicity, re
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德國康佳強力脈通 Asekivex 60粒, 強力脈通Heibuken Strong Maton 100粒, 心腦素 Adenosine Triphospat 100粒, 血脈素 Adenosine Triphosphat 100粒, 高樂
Read 15 responses to: My 10 year old daughter has what appears to be... Find the best answer on Mamapedia - mom trusted since 2006.

Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 [Report Updated: 14022018] Prices from USD $1250 - BioPortfolio.comAdenosine A2 Receptor Antagonist Pipeline Insight, 2018 [Report Updated: 14022018] Prices from USD $1250 - BioPortfolio.com

Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 report by DelveInsight offers comprehensive insights of the pipeline ... Pipeline Therapeutics assessment of products for Adenosine A2 Receptor Antagonist The report assesses the active Adenosine A2 ... Adenosine A2 Receptor Antagonist Pipeline Insight, 2018 [Report Updated: 14022018] Prices from USD $1250. 02:34 EDT 21 Mar 2018 ... Features the Adenosine A2 Receptor Antagonist pipeline across the complete product development cycle including all clinical and ...
more infohttps://www.bioportfolio.com/news/article/3573619/Adenosine-A2-Receptor-Antagonist-Pipeline-Insight-2018-Report-Updated-14022018-Prices-from.html

BIIB014 Phase 2a Monotherapy - Full Text View - ClinicalTrials.govBIIB014 Phase 2a Monotherapy - Full Text View - ClinicalTrials.gov

Adenosine A2 Receptor Antagonists. Purinergic P1 Receptor Antagonists. Purinergic Antagonists. Purinergic Agents. ... Participation in a previous adenosine A2A trial.. *Participation in any other investigational drug study within 1 month prior ...
more infohttps://clinicaltrials.gov/ct2/show/NCT00451815?term=biogen&spons=biogen&rank=18

Using PET Scans to Study Brain Receptor Occupancy of BIIB014 in Healthy Male Volunteers - Full Text View - ClinicalTrials.govUsing PET Scans to Study Brain Receptor Occupancy of BIIB014 in Healthy Male Volunteers - Full Text View - ClinicalTrials.gov

Adenosine A2 Receptor Antagonists. Purinergic P1 Receptor Antagonists. Purinergic Antagonists. To Top ... An Open-Label, Positron Emission Tomography Study to Assess Adenosine A2A Brain Receptor Occupancy of BIIB014 at Multiple Dose ... occupies the brains A2A receptors. Receptor occupancy will be assessed by PET scanning using a radiolabelled tracer. ... Using PET Scans to Study Brain Receptor Occupancy of BIIB014 in Healthy Male Volunteers. The safety and scientific validity of ...
more infohttps://clinicaltrials.gov/ct2/show/NCT00531193

Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed...Physiological roles of A1 and A2A adenosine receptors in regulating heart rate, body temperature, and locomotion as revealed...

... were studied in awake mice lacking one or both of the adenosine A(1) or A(2A) receptors (A(1)R or A(2A)R, respectively) using ... indicating effects of endogenous adenosine. The A(2A)R plays an important role in the modulation of O(2)C and LA by acute and ... Modulation of paracetamol antinociception by caffeine and by selective adenosine A2 receptor antagonists in mice.. *Lisa ... Selective Deletion of the A1 Adenosine Receptor Abolishes Heart-Rate Slowing Effects of Intravascular Adenosine In Vivo. * ...
more infohttps://www.semanticscholar.org/paper/Physiological-roles-of-A1-and-A2A-adenosine-in-body-Yang-Chen/462ed1bcc5b5b1847b0a4a38c0ad02de3c3ee91b

Drug CategoriesBrowse DrugBank Categories - DrugBankDrug CategoriesBrowse DrugBank Categories - DrugBank

Adenosine A2 Receptor Antagonists. Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS.. 4. ... Adenosine A2 Receptor Agonists. Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS.. 4. 3. Details. ... Adenosine A1 Receptor Agonists. Not Available. 1. 0. Details. Adenosine A1 Receptor Antagonists. Compounds that bind to and ... Drugs that inhibit ADENOSINE DEAMINASE activity.. 1. 1. Details. Adenosine Kinase, antagonists & inhibitors. Not Available. 1. ...
more infohttps://www.drugbank.ca/categories?page=4

Indobufen Sodium | Semantic ScholarIndobufen Sodium | Semantic Scholar

Binding of [3H]KF17837S, a selective adenosine A2 receptor antagonist, to rat brain membranes. ... The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors ... Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A3 receptor subtype. ... N3,N7-diaminophenothiazinium derivatives as antagonists of α7-nicotinic acetylcholine receptors expressed in Xenopus oocytes. ...
more infohttps://www.semanticscholar.org/topic/Indobufen-Sodium/5197831

Diprophylline - WikipediaDiprophylline - Wikipedia

Schwabe, U; Ukena, D; Lohse, MJ (September 1985). "Xanthine Derivatives as Antagonists at A1 and A2 Adenosine Receptors". ... It acts as an adenosine receptor antagonist and phosphodiesterase inhibitor. Xanthine "International Non-Proprietary Names. ...
more infohttps://en.wikipedia.org/wiki/Diprophylline

Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative DisordersRole of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders

Caffeine portrays its activity as adenosine A2 receptor antagonist which results in enhanced loco motor activity in ... It directs the down-regulation of adenosine A2 receptors to counter the suppressive effect of adenosine on brain dopaminergic ... Rivera-Oliver M, Díaz-Ríos M. Using caffeine and other adenosine receptor antagonists and agonists as therapeutic tools against ... As the Caffeine exerts a potential efficacy to act as antagonist of adenosine receptor, thus it potentially reduces ...
more infohttp://www.ijbs.com/v14p0341.htm

Search Articles | University of Toronto LibrariesSearch Articles | University of Toronto Libraries

Adenosine A1 Receptor Antagonists - metabolism , Adenosine A2 Receptor Antagonists - metabolism , Adenosine A2 Receptor ... Receptor, Adenosine A2A - metabolism , Adenosine A2 Receptor Antagonists - pharmacology , Animals , Adenosine A2 Receptor ... Receptor, Adenosine A2A - drug effects , Adenosine A2 Receptor Antagonists - pharmacology , Adenosine A2 Receptor Agonists - ... Receptor heteromer , C-FOS EXPRESSION , Adenosine A2 Receptor Antagonists - pharmacology , Animals , Adenosine A2 Receptor ...
more infohttps://query.library.utoronto.ca/index.php/search/q?kw=SubjectTerms:Adenosine%20A2%20Receptor%20Antagonists%20-%20pharmacology

A Category Names List - Drug Information Portal - U.S. National Library of MedicineA Category Names List - Drug Information Portal - U.S. National Library of Medicine

Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Antagonists (8) • Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS. ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ...
more infohttps://druginfo.nlm.nih.gov/drugportal/drug/categories

A Category Names List - Drug Information Portal - U.S. National Library of MedicineA Category Names List - Drug Information Portal - U.S. National Library of Medicine

Adenosine A2A Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2A Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2B Receptor Agonists (0) see Adenosine A2 Receptor Agonists. Adenosine A2B Receptor Antagonists (0) see Adenosine A2 ... Adenosine A2 Receptor Antagonists (8) • Compounds that selectively bind to and block the activation of ADENOSINE A2 RECEPTORS. ... Adenosine A2 Receptor Agonists (4) • Compounds that selectively bind to and activate ADENOSINE A2 RECEPTORS. MeSH ...
more infohttps://druginfo.nlm.nih.gov/drugportal/jsp/drugportal/drugNamesAndCategories.jsp

Patent US8114147 - Continuous double layered stent for migration resistance - Google PatentsPatent US8114147 - Continuous double layered stent for migration resistance - Google Patents

... selective adenosine A1 antagonists, adenosine A2 receptor antagonists (e.g., CGS 21680, regadenoson, UK 432097 or GW 328267), ... beta receptor antagonists (e.g., atenolol, metaprolol and butoxamine), angiotensin-II receptor antagonists (e.g., losartan, ... o) leukotriene receptor antagonists; (p) antagonists of E- and P-selectins;. *(q) inhibitors of VCAM-1 and ICAM-1 interactions; ... receptor antagonists and chimeric fusion proteins, TNF-α pathway agents such as thalidomide and analogs thereof, Thromboxane A2 ...
more infohttp://www.google.com/patents/US8114147?dq=7,053,767

KAKEN - Research Projects | Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal...KAKEN - Research Projects | Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal...

Moreover, CHA, an adenosine A1 receptor antagonist and CGS-21680, an adenosine A2 receptor antagonist, were also effective in ... adenosine / dementia / gerbil / ischemia / neuroprotection / primary culture / adenosine / AMP / ATP / A1 receptor / cortex / ... This selective damage was attenuated by MK-801, a NMDA receptor antagonist and L-NAME, a nitric oxide synthase inhibitor. ... This cell death was attenuated by treatment of MK-801, L-NAME, adenosine, CHA and CGS-21680. CHA reduced hypoxia/hypoglycemia- ...
more infohttps://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14572088/

JCI -
The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte...JCI - The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte...

... completely reversed by a specific adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), but not affected ... by an adenosine A1 receptor antagonist, 8-cyclopentyl-dipropylxanthine. Neither ADA nor DMPX affected leukocyte accumulation in ... Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation.. B N ... Methotrexate, a folate antagonist, is a potent antiinflammatory agent when used weekly in low concentrations. We examined the ...
more infohttps://www.jci.org/articles/view/116884

CGS-15943 - WikipediaCGS-15943 - Wikipedia

"Comparison of the behavioural effects of an adenosine A1/A2-receptor antagonist, CGS 15943A, and an A1-selective antagonist, ... CGS-15943 is a drug which acts as a potent and reasonably selective antagonist for the adenosine receptors A1 and A2A, having a ... It was one of the first adenosine receptor antagonists discovered that is not a xanthine derivative, instead being a ... Holtzman SG (1991). "CGS 15943, a nonxanthine adenosine receptor antagonist: effects on locomotor activity of nontolerant and ...
more infohttps://en.wikipedia.org/wiki/CGS-15943

Ronald Pearl | Stanford Medicine ProfilesRonald Pearl | Stanford Medicine Profiles

... results consistent with an adenosine A2 receptor. Pretreatment with the adenosine A1 receptor antagonist ... and pretreatment with the adenosine A2 receptor antagonist CGS 15943A increased the ED50 of NECA to 2.7 x 10(-7) mol/L. These ... ADENOSINE PRODUCES PULMONARY VASODILATION IN THE PERFUSED RABBIT LUNG VIA AN ADENOSINE A(2) RECEPTOR ANESTHESIA AND ANALGESIA ... results suggest that adenosine produces pulmonary vasodilation via activation of an adenosine A2 receptor. ...
more infohttps://med.stanford.edu/profiles/ronald-pearl

Synthesis, Antibacterial Activity and DFT Calculation of Naphtopyrano, Furo and Pyrazolo [3,2,e] [1,2,4]Triazolo-[1,5-c...Synthesis, Antibacterial Activity and DFT Calculation of Naphtopyrano, Furo and Pyrazolo [3,2,e] [1,2,4]Triazolo-[1,5-c...

... new potent adenosine A2 receptor antagonists. Eur J Med Chem 28(7-8):569-576. https://doi.org/10.1016/0223-5234(93)90087-U ... and biodistribution of a new potent and selective ligand for in vivo imaging of the adenosine A2A receptor system using ... pyrimidines as inhibitors of receptor tyrosine kinases (RTK). Helv Chim Acta 87(4):956-975. https://doi.org/10.1002/hlca. ...
more infohttps://link.springer.com/article/10.1007%2Fs42250-019-00081-y

WO2011034768A1 - Integrated stent retrieval loop adapted for snare removal and/or optimized purse stringing 
        - Google...WO2011034768A1 - Integrated stent retrieval loop adapted for snare removal and/or optimized purse stringing - Google...

... selective adenosine Al antagonists, adenosine A2 receptor antagonists (e.g., CGS 21680, regadenoson, UK 432097 or GW 328267), ... antagonists such as propranolol and α/β-antagonists such as labetalol and carvedilol; (e) endothelin receptor antagonists such ... beta receptor antagonists (e.g., atenolol, metaprolol and butoxamine), angiotensin-II receptor antagonists (e.g., losartan, ... o) leukotriene receptor antagonists; (p) antagonists of E- and P-selectins; (q) inhibitors of VCAM-1 and ICAM-1 interactions; ( ...
more infohttps://patents.google.com/patent/WO2011034768A1/en

Patients being sought for clinical trial treating weak respiratory muscles after spinal cord injuryPatients being sought for clinical trial treating weak respiratory muscles after spinal cord injury

Nantwi KD and Goshgarian HG (2002). Actions of specific adenosine receptor A1 and A2 agonists and antagonists in recovery of ... a general adenosine A1 and A2 receptor antagonist, can activate the latent pathway by acting centrally through antagonism at ... adenosine receptors. 2. The present study was designed to assess the relative contributions of adenosine A1 and A2 receptors in ... To further test the involvement of adenosine receptors, N6 (L-2-phenylisopropyl) adenosine (L-PIA), an analogue of adenosine ...
more infohttp://sci.rutgers.edu/forum/showthread.php?38417-Patients-being-sought-for-clinical-trial-treating-weak-respiratory-muscles-after-spinal-cord-injury&s=499442ae1ab1cc6490474666da3282dd

Dyphylline - DrugBankDyphylline - DrugBank

Schwabe U, Ukena D, Lohse MJ: Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch ... Schwabe U, Ukena D, Lohse MJ: Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch ... Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.. Gene Name. ... Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.. Gene Name. ...
more infohttps://www.drugbank.ca/drugs/DB00651

neurophysiology - How does caffeine work as an analgesic adjuvant? - Psychology & Neuroscience Stack Exchangeneurophysiology - How does caffeine work as an analgesic adjuvant? - Psychology & Neuroscience Stack Exchange

Caffeine is a nonselective antagonist of adenosine A1 and A2 receptors. Adenosine A2a receptors induce intracellular signalling ... disinhibition of inhibitory adenosine actions on central cholinergic nerve terminals, leading to increased acetylcholine ... a blockade of peripheral pro-nociceptive actions of adenosine;. *the activation of the central noradenosine, pain-suppressing ...
more infohttps://psychology.stackexchange.com/questions/20758/how-does-caffeine-work-as-an-analgesic-adjuvant

Akamatsu Hiroshi - Inventor Patent Directory, Page 1Akamatsu Hiroshi - Inventor Patent Directory, Page 1

That is, it provides a novel condensed imidazole compound which has an adenosine A2 receptor antagonist action, ... ... which is a new type based on an adenosine A2 receptor antagonist action. ... Matsushita Electric, December 22, 2004: EP1488880-A2 (2 worldwide citation) A structure of solder joint structure formed of ...
more infohttp://patent.ipexl.com/inventor/akamatsu_hiroshi_1.html

Basal Forebrain Histaminergic Transmission Modulates Electroencephalographic Activity and Emergence from Isoflurane Anesthesia ...Basal Forebrain Histaminergic Transmission Modulates Electroencephalographic Activity and Emergence from Isoflurane Anesthesia ...

... deprivation on righting reflex in the rat is partially reversed by administration of adenosine A1 and A2 receptor antagonists. ... H1 receptor antagonist triprolidine and H2 receptor antagonist cimetidine had no effect on the breathing rate during isoflurane ... selective H1 receptor antagonist triprolidine (5 μg/1 μl), or selective H2 receptor antagonist cimetidine (25 μg/1 μl) alone 30 ... Antagonists of H1 and H2 receptors were infused directly into the NBM to reveal the specific receptor underlying the ...
more infohttp://anesthesiology.pubs.asahq.org/article.aspx?articleid=1932220

Respiratory Pharmacology by Chris Arakawa on PreziRespiratory Pharmacology by Chris Arakawa on Prezi

Nonselective adenosine receptor antagonist (Blocks A1, A2, A3 equally). Mechanism: Nonspecific AChRi -,promotes degrdation of ...
more infohttps://prezi.com/h0ofaqeloe0w/respiratory-pharmacology/

Molecular probes for adenosine receptors - Patent # 5248770 - PatentGeniusMolecular probes for adenosine receptors - Patent # 5248770 - PatentGenius

These probes bind to A.sub.2 and A.sub.3 adenosine receptors and aid in quantifying and characterizing the receptors. The ... This application discloses probes for adenosine receptors which are functionalized congeners of the following compound: ##STR1# ... which are antagonists for A-1 and A-2 receptors, these probes are prepared by reacting a fluorescent dye marker, or electron ... Both adenosine and xanthine derivatives bind competitively to A-1 and A-2 adenosine receptors.. UTILITY STATEMENT. The present ...
more infohttp://www.patentgenius.com/patent/5248770.html
  • 5 Histamine acts on G-protein coupled receptors in the brain, with H1 and H2 receptors mainly exciting the postsynaptic membrane and H3 receptors suppressing the presynaptic release of histamine and other neurotransmitters. (asahq.org)
  • A cDNA encoding a G protein-coupled receptor of unknown ligand specificity was isolated from a human hippocampal cDNA library by virtue of the high degree of structural homology between members of this receptor family. (garvan.org.au)
  • Although CCR7(-/-) naive T cells displayed a small reduction in locomotion, systemic treatment with pertussis toxin reduced naive T lymphocyte speed by 59%, indicating a contribution of Galpha(i)-mediated signaling, but involvement of other G protein-coupled receptors besides CCR7. (ox.ac.uk)
  • These data implicate pO(2), tissue architecture, and G-protein coupled receptor signaling in regulation of naive T lymphocyte migration in explanted LNs. (ox.ac.uk)
  • Moreover, this results rise the possibility that adenosine becomes a drug for the dementia induced by vascular damage. (nii.ac.jp)
  • Methotrexate, a folate antagonist, is a potent antiinflammatory agent when used weekly in low concentrations. (jci.org)
  • Pharmacologically relevant doses of methotrexate increased splenocyte AICAR content, raised adenosine concentrations in exudates from carrageenan-inflamed air pouches, and markedly inhibited leukocyte accumulation in inflamed air pouches. (jci.org)
  • Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of Wistar rats? (ovid.com)
  • This study aims to evaluate adenosine and P2 receptors and cellular signalling in cardiac arrest produced by purines in the heart. (ovid.com)
  • Cumulative concentration-effect curves of adenosine and CPA resulted in a negative chronotropic effect culminating in cardiac arrest at 1000 μM (adenosine) and 1 μM (CPA). (ovid.com)
  • 4-Aminopyridine, a blocker of potassium channels at 10 mM, prevented the cardiac arrest produced by adenosine and ATP, while BayK 8644, activator of calcium channels, did not prevent cardiac arrest. (ovid.com)
  • We examined the hypothesis that the antiphlogistic effects of methotrexate result from its capacity to promote intracellular accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) that, under conditions of cell injury, increases local adenosine release. (jci.org)
  • Additionally, adenosine receptor antagonists blocked mGluR-mediated increases in cAMP accumulation with potencies that were highly correlated with their potencies at A2 adenosine receptors. (jneurosci.org)
  • The present invention provides a preventive or therapeutic agent for diabetes mellitus and diabetic complications, which is a new type based on an adenosine A2 receptor antagonist action. (ipexl.com)
  • The present application prepares and describes probes radioactive and non-radioactive for more sensitive assay-type quantitative binding measurements of A-1 and A-2 receptors using the functionalized congeners described and claimed in the fourabove-named copending applications. (patentgenius.com)
  • These results indicate that methotrexate is a nonsteroidal antiinflammatory agent, the antiphlogistic action of which is due to increased adenosine release at inflamed sites. (jci.org)
  • Autonomic nerves release ATP, which is processed into adenosine in the synaptic cleft. (ovid.com)