Pharmacological effects of Ro 22-1319: a new antipsychotic agent.
Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of antipsychotic agents. The avoidance-blocking potency of Ro 22-1319 (0.7 mg/kg) in this procedure approached that of haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of chlorpromazine and clozapine, respectively. Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of apomorphine emesis in dogs. High potency and antipsychotic-like activity have been demonstrated in monkey EEG and in an in vivo 3H-spiroperidol binding assay. Although studies of amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites, Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that Ro 22-1319 is an efficacious antipsychotic compound, almost as potent as haloperidol, with fewer or less intense extrapyramidal effects and low potential for tardive dyskinesia.
D000661:Amphetamine / Q000037:antagonists & inhibitors; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D004285:Dogs; D004298:Dopamine / Q000502:physiology; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D012453:Saimiri; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D007546:Isoquinolines; D000661:Amphetamine; D001058:Apomorphine; C032412:Ro 22-1319; D004298:Dopamine