Correlation between antiavoidance activities of antipsychotic drugs in rats and daily clinical doses

Abstract

Effects of oral antipsychotic drugs, 12 phenothiazines, 3 thioxanthenes, 5 butyrophenones and 8 other derivatives on Sidman and discriminated avoidance responses in rats were investigated and compared to their clinical doses routinely used PO. Almost all drugs except sulpiride and clozapine suppressed the avoidance responses with a dose-dependent decrease in the response rate (lever-pressing) and increase in the shock rate in the Sidman avoidance performance or a decrease in both the response and avoidance rates in the discriminated one. Sulpiride (80-640 mg/kg) produced no marked change in the avoidance responses. Clozapine (2.5-10 mg/kg) increased the shock rate or decreased the avoidance rate without eliciting any change in the response rate. The avoidance-suppressing activities of the antipsychotic drugs were well correlated with their clinical daily doses. However, the avoidance-suppressing effects of carpipramine, clocapramine, thiothixene and sulpiride were relatively less potent, while that of clotiapine was more potent than in the clinical activities. The potencies of the avoidance-suppressing effects of each drug on the Sidman and the discriminated avoidance responses were almost identical except for triflupromazine, pimozide, thioridazine, spiclomazine and propericiazine. The former two drugs suppressed the Sidman avoidance response more than the discriminated avoidance response. However, the latter three drugs suppressed the discriminated avoidance response more markedly than the Sidman avoidance response. The present results suggest that the avoidance response in rats is applicable in evaluating the clinical efficacies of antipsychotic drugs.