Seroquel: behavioral effects in conventional and novel tests for atypical antipsychotic drug.
Seroquel was compared to clozapine and several other antipsychotic agents in tests predictive of antipsychotic activity or extrapyramidal symptoms. In the conditioned avoidance test in squirrel monkeys as well as several paradigms using apomorphine or amphetamine-induced behavioral alterations, seroquel displayed the profile of a drug with potential antipsychotic activity. In these paradigms the potency of seroquel was somewhat less than clozapine in rodent tests, while the reverse was true in higher species, i.e. monkeys, cats. In tests designed to evaluate the propensity to induce EPS or tardive dyskinesia, for example, the production of dyskinetic reactions in haloperidol-sensitized cebus monkeys, seroquel displayed a profile similar to clozapine and disparate from typical antipsychotic drugs. In drug-naive cebus monkeys seroquel sensitized significantly fewer monkeys than haloperidol and the dyskinetic reactions were of significantly less intensity. It is anticipated that this novel antipsychotic agent will have a significantly reduced propensity to produce extrapyramidal symptoms and tardive dyskinesia than typical antipsychotics.
Migler
B M
BM
ICI Pharmaceuticals Group, Department of Chemistry, ICI Americas Inc., Wilmington, DE 19897.
Warawa
E J
EJ
Malick
J B
JB
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D002415:Cats; D002428:Cebus; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005260:Female; D005403:Fixation, Ocular / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D012453:Saimiri; D013239:Stereotyped Behavior / Q000187:drug effects; D013550:Swimming
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D000661:Amphetamine; D001058:Apomorphine