Evidence that the different properties of haloperidol and clozapine are not explained by differences in anticholinergic potency

Abstract

In previous studies we have shown that neuroleptic drugs are distinctly different in their ability to antagonize apomorphine-induced behavioural activation. Comparison with clinical data indicated that antipsychotic drugs causing extrapyramidal side effects (EPS), like haloperidol, efficiently antagonized apomorphine-induced gnawing and in higher doses also apomorphine-induced locomotion, while drugs with a low incidence of EPS, like clozapine, antagonized only locomotion, sniffing, and repetitive head and limb movements, and could even potentiate the gnawing. The difference between haloperidol and clozapine in the incidence of EPS has been tentatively explained by the fact that clozapine has an anticholinergic action apart from its ability to block dopamine receptors. As an indirect test of this hypothesis we have made use of the difference in the ability to antagonize apomorphine-induced behaviour and tested whether a combination of haloperidol and an anticholinergic drug (scopolamine) can mimick the characteristic effect of clozapine on apomorphine-induced behaviour. We found that the pattern of behaviour elicited by apomorphine after combined haloperidol and scopolamine pretreatment was characterized by sniffing and repetitive head and limb movements. This patter of behaviour showed a clear dose-response characteristic in that the intensity of the stereotypies was increased with increasing doses of scopolamine. However, it was not possible to induce strong compulsive gnawing, which is pattern of behaviour elicited by apomorphine after high doses of clopazine. These results therefore support the idea that the different properties of haloperidol and clozapine cannot be explained by differences in anticholinergic potencies.