Activity of "seroquel" (ICI 204,636) in animal models for atypical properties of antipsychotics: a comparison with clozapine.
The pharmacologic treatment of schizophrenia still suffers from two major problems: (1) most antipsychotic drugs still induce severe neurologic (extrapyramidal) side effects; (2) few antipsychotic drugs are effective in treating the negative symptoms of schizophrenia. In the present study, we have evaluated the effects of ICI 204,636 in the rat paw test and the amphetamine-induced social isolation in monkeys and compared them with the effects of clozapine. The paw test has been shown to be a valid model for differentiating classic and atypical neuroleptic drugs. The monkey social isolation model seems to represent one of the few animal models with validity for the negative symptoms of schizophrenia. The results show that both ICI 204,636 and clozapine had the profile of an atypical antipsychotic in the paw test, suggesting a reduced propensity to induce extrapyramidal side effects in humans. Likewise, ICI 204,636 and clozapine were found to prevent the amphetamine-induced social isolation in monkeys, suggesting a good therapeutic effect mitigating the negative symptoms in schizophrenia. Overall, the data suggest that ICI 204,636 may represent a new and interesting antipsychotic drug, closely resembling clozapine.
Ellenbroek
B A
BA
Department of Psychoneuropharmacology, University of Nijmegen, The Netherlands.
Lubbers
L J
LJ
Cools
A R
AR
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008251:Macaca; D008297:Male; D000069348:Quetiapine Fumarate; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy*; D012919:Social Behavior
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D003024:Clozapine