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Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing: Evidence for two different mechanisms of action

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Abstract

Apomorphine 5 mg/kg given s.c. induces two different behaviours that can be separately measured in a special test box: one characterized by increased locomotion and one characterized by strong compulsive gnawing. Six different neuroleptic drugs with different clinical profiles (metaclopramide, haloperidol, chlorpromazine, thioridazine, clozapine, and sulpiride) were tested for their ability to antagonize either of these two different behaviours. We found that the neuroleptic drugs causing high incidences of extrapyramidal side effects (metoclopramide and haloperidol) predominantly antagonized the apomorphine-induced compulsive gnawing, while the ‘atypical’ neuroleptic drugs causing low incidences of extrapyramidal side effects (thioridazine, clozapine, sulpiride) instead antagonized the apomorphine-induced locomotion. When the drugs were rank-ordered according to their relative potencies in antagonizing gnawing as compared to locomotion, the rank order paralleled clinical data concerning the incidence of extrapyramidal side effects. The findings are tentatively explained by the existence of two different dopamine receptors. The test may be useful for the screening of new neuroleptic drugs because it seems possible to distinguish drugs producing extrapyramidal side effects from drugs that do not.

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  1. Department of Histology, Karolinska Institutet, Stockholm, Sweden

    T. Ljungberg & U. Ungerstedt

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  1. T. Ljungberg
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  2. U. Ungerstedt
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Ljungberg, T., Ungerstedt, U. Classification of neuroleptic drugs according to their ability to inhibit apomorphine-induced locomotion and gnawing: Evidence for two different mechanisms of action. Psychopharmacology 56, 239–247 (1978). https://doi.org/10.1007/BF00432845

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