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Differential antagonism of antiavoidance, cataleptic and ptotic effects of neuroleptics by biperiden.

The interaction between neuroleptics and an anticholinergic, biperiden, in the antiavoidance, catalepsy and ptosis tests was investigated in mice for the purpose of predicting the extrapyramidal side-effects of neuroleptics. The cataleptic effect of most neuroleptics used was antagonized to some extent by biperiden, while the ptotic effect was hardly influenced. The antiavoidance effect of haloperidol, trifluperidol and perphenazine was markedly antagonized and that of chlorpromazine moderately. However, the effect of thioridazine, chlorprothixene, levomepromazine and clozapine was little antagonized. In neuropharmacological tests, haloperidol, trifluperidol and perphenazine exhibited a selective antidopaminergic activity, while chlorprothixene, levomepromazine and clozapine showed antidopaminergic, antiadrenergic and also anticholinergic activities when similar doses were given. These results indicate that biperiden antagonism may be marked in the tests related to the extrapyramidal symptoms and in drugs liable to induce extrapyramidal side effects, however, there would be little or no antagonism in drugs possessing the anticholinergic property and eliciting few extrapyramidal side-effects.