Biomaterial Database

Binding profile of the novel 5-HT1B/1D receptor antagonist, [3H]GR 125,743, in guinea-pig brain: a comparison with [3H]5-carboxamidotryptamine. 1997

V Audinot, and S Lochon, and A Newman-Tancredi, and G Lavielle, and M J Millan

Institut de Recherches Servier, Department of Psychopharmacology, Croissy-sur-Seine, France.

Native brain 5-HT1B/1D) receptors were studied using the novel antagonist, [3H]GR 125,743 (N-[4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]-3-methyl-4-(4-pyri dyl)benzamide). In guinea-pig striatal membranes, [3H]GR 125,743 displayed rapid association (t1/2 = 4.5 min), high (90%) specific binding and high affinity (K(d) = 0.29 nM), although B(max) values (fmol/mg protein) varied according to brain region-striatum: 199; frontal cortex: 89; hippocampus: 79; cerebellum: 26. In frontal cortex, the B(max) determined with [3H]5-CT ([3H]carboxamidotryptamine) was significantly higher (178; P < 0.05), suggesting that it also labels other binding sites. In striatal membranes, guanylylimidodiphosphate (GppNHp) inhibited [3H]5-CT but not [3H]GR 125,743 binding, suggesting that the latter has antagonist properties. Nevertheless, in competition binding experiments, the pK(i) values obtained with [3H]GR 125,743 and [3H]5-CT for 20 serotonergic ligands, including L 694,247 (2-[5-[3-(4-methylsulphonylamino)benzyl-1,2,4-oxadiazol-5-yl ]-1H-indole-3-yl]ethylamine), GR46,611 (3-[3-(2-dimethylamino-ethyl)-1H-indol-6-yl]-N-(4-methoxybenzyl)acrylami de), sumatriptan and alniditan, were highly correlated (r = 0.99). Ketanserin and ritanserin showed low affinity for [3H]GR 125,743 binding to guinea-pig striatal sites (K(i) = 12600 and 369 nM), suggesting that 5-HT1B (rather than 5-HT1D) receptors are predominantly labelled in this tissue. The present data indicate that [3H]GR 125,743 is a useful tool for studying native 5-HT1B/1D receptors.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D001921	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.	Encephalon
D006168	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.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001549	Benzamides	BENZOIC ACID amides.
D001667	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.	Competitive Binding
D012701	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.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D012702	Serotonin Antagonists	Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.	5-HT Antagonist,5-HT Antagonists,5-Hydroxytryptamine Antagonist,5-Hydroxytryptamine Antagonists,Antiserotonergic Agent,Antiserotonergic Agents,Serotonin Antagonist,Serotonin Blockader,Serotonin Blockaders,Serotonin Receptor Antagonist,Serotonin Receptor Blocker,Antagonists, 5-HT,Antagonists, 5-Hydroxytryptamine,Antagonists, Serotonin,Serotonin Receptor Antagonists,Serotonin Receptor Blockers,5 HT Antagonist,5 HT Antagonists,5 Hydroxytryptamine Antagonist,5 Hydroxytryptamine Antagonists,Agent, Antiserotonergic,Agents, Antiserotonergic,Antagonist, 5-HT,Antagonist, 5-Hydroxytryptamine,Antagonist, Serotonin,Antagonist, Serotonin Receptor,Antagonists, 5 HT,Antagonists, 5 Hydroxytryptamine,Antagonists, Serotonin Receptor,Blockader, Serotonin,Blockaders, Serotonin,Blocker, Serotonin Receptor,Blockers, Serotonin Receptor,Receptor Antagonist, Serotonin,Receptor Antagonists, Serotonin,Receptor Blocker, Serotonin,Receptor Blockers, Serotonin
D017366	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.	5-HT Agonists,5-Hydroxytryptamine Agonists,Serotonin Agonists,5-HT Agonist,5-Hydroxytrytamine Agonist,Receptor Agonists, Serotonin,Serotonergic Agonist,Serotonergic Agonists,Serotonin Agonist,Serotonin Receptor Agonist,5 HT Agonist,5 HT Agonists,5 Hydroxytryptamine Agonists,5 Hydroxytrytamine Agonist,Agonist, 5-HT,Agonist, 5-Hydroxytrytamine,Agonist, Serotonergic,Agonist, Serotonin,Agonist, Serotonin Receptor,Agonists, 5-HT,Agonists, 5-Hydroxytryptamine,Agonists, Serotonergic,Agonists, Serotonin,Agonists, Serotonin Receptor,Receptor Agonist, Serotonin