Pharmacological and biochemical studies on a new potential neuroleptic, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050).
Pharmacological and biochemical properties of a novel compound, N-(1-benzyl-3-pyrrolidinyl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-08050) were compared with those of haloperidol (HPD) and chlorpromazine (CPZ) in animals. YM-08050 was more potent than either HPD or CPZ in inhibitory effects on a variety of behaviors such as apomorphine-induced stereotypes behavior and emesis, methamphetamine-induced stereotyped behavior, conditioned avoidance response and open field behavior. YM-08050 induced catalepsy only at much higher doses than to exhibit the inhibitory activities. The inhibitory effects of YM-08050 on [3H]dopamine binding and dopamine-sensitive adenylate cyclase in the synaptic membrane fractions of canine caudate nucleus were much greater than those of HPD and CPZ. The results suggest that YM-08050, a potent central dopaminergic blocker, is a potential antipsychotic drug with less extrapyramidal side effects than those of HPD and CPZ.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001549:Benzamides / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced; D002746:Chlorpromazine / Q000494:pharmacology; D004285:Dogs; D004298:Dopamine / Q000378:metabolism; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors; D051379:Mice; D010830:Physostigmine / Q000633:toxicity; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D013570:Synaptic Membranes / Q000378:metabolism
D014150:Antipsychotic Agents; D001549:Benzamides; D008694:Methamphetamine; C022913:YM-08050; D010830:Physostigmine; D006220:Haloperidol; D001058:Apomorphine; D002746:Chlorpromazine; D004298:Dopamine