Anticholinergic activity of antipsychotic drugs in relation to their extrapyramidal effects

Antipsychotic drugs were evaluated with two indices of anticholinergic activity, mydriasis in mice in vivo and antagonism of carbamylcholine-induced contractions of guinea-pig tracheal strips in vitro. The drugs from most to least potent as oral mydriatic agents were mepazine, clozapine, thioridazine, promazine and chlorpromazine. Trifluoperazine, pimozide and haloperidol were inactive. These results were consistent with the hypothesis that anticholinergic activity of antipsychotic drugs is inversely related to their propensity to produce extrapyramidal effects in man. In vitro results appeared to predict the incidence of extraphyramidal effects less accurately than in vivo results.