Effects of the novel antipsychotics, RMI 81582 and clopipazan, on predictors of extrapyramidal liability in squirrel monkeys

Publisher Website
Google Scholar
Abstract
The neuroleptic‐induced acute dyskinetic syndrome in primates has been proposed as a predictor for extrapyramidal side effects of potential antipsychotics. Another potential predictor in monkeys is the degree to which benztropine reverses antipsychotic‐induced inhibition of Sidman avoidance performance. Assessment of these models has been hampered by the scarcity of clinically effective antipsychotics that lack extrapyramidal side effects. Recently, however, RMI 81582 and clopipazan have been reported to exert antipsychotic activity in initial clinical trials without causing extrapyramidal side effects. Using squirrel monkeys, these drugs were tested in both procedures. RMI 81582 did not cause dyskinesias at any dose tested, and its blockade of avoidance could not be antagonized by benztropine. These results are consistent with the previously proposed clozapine‐like profile of RMI 81582. However, clopipazan, like haloperidol, induced dyskinesias and its effects on avoidance were reversed by benztropine. Possible clinical implications are discussed. These results support the predictive value of these two primate models for antipsychotic‐induced extrapyramidal dysfunction.