Cataleptogenic effect of subtype selective 5-HT receptor antagonists in the rat. 1998

H O Kalkman, and V Neumann, and J Nozulak, and M D Tricklebank
Nervous System Research, Novartis Pharma Inc., Basel, Switzerland.

5-HT receptor antagonists with selectivity for 5-HT1A WAY-100635 (N-[2-[-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide), 5-HT1B GR 127935 (N-[methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'(5-methyl-1,2, 4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide x HCl), 5-HT2C SB 200646A (N-(1-methyl-5-indolyl)-N'-(3-pyridyl)urea x HCl) and 5-HT2A (ketanserin, fananserin and MDL 100,151 ((+/-)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipe ridinemethanol) receptors were tested for cataleptogenic responses in rats. WAY-100635 (0.1-3 mg/kg, s.c.), ketanserin (0.1-3 mg/kg, s.c.), MDL 100,151 (0.3-3 mg/kg, s.c.) and fananserin (RP 62203; 3 mg/kg, s.c.) induced a significant catalepsy. GR 127935 (1 mg/kg, s.c.), SB 200646A (without effect per se at 10 mg/kg, s.c.) and MDL 100,151 (0.3 mg/kg, s.c.) did not inhibit the cataleptic response to the dopamine D2 receptor antagonist, loxapine (0.3 mg/kg, s.c.). Catalepsy induced by MDL 100,151 (3 mg/kg) was blocked by co-treatment with clozapine, but not by SB 200646A (both at 10 mg/kg, s.c.). Although clozapine displays significant affinity to 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors, the present results suggest that blockade of these receptors is not responsible for clozapine's anticataleptic activity.

UI MeSH Term Description Entries
D008297 Male Males
D011985 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. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D002375 Catalepsy A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions. Cerea Flexibilitas,Flexibility, Waxy,Anochlesia,Anochlesias,Catalepsies,Flexibilitas, Cerea,Flexibilities, Waxy,Waxy Flexibilities,Waxy Flexibility
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
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
D017208 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. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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