Clozapine versus Perphenazine: The Value of the Biochemical Mode of Action of Neuroleptics in Predicting their Therapeutic Activity
- 1 December 1976
- journal article
- clinical trial
- Published by Royal College of Psychiatrists in The British Journal of Psychiatry
- Vol. 129 (6), 547-555
- https://doi.org/10.1192/bjp.129.6.547
Abstract
Summary: The chemical structure of a neuroleptic does not reliably predict the exact profile of its therapeutic action. We considered the question whether the biochemical action of a neuroleptic, and specifically the ratio between DA-receptor block and NA-receptor block, might have a higher predictive value in this respect. In this context we carried out a double-blind study of the therapeutic value of clozapine and perphenazine in acute psychoses of varying symptomatology and aetiology. There are strong indications that clozapine has only a slight inhibitory effect on transmission in central DA-ergic neurons, but markedly inhibits transmission in central NA-ergic neurons, and that the reverse applies to perphenazine. In view of these data we expected perphenazine to be a stronger antipsychotic and a weaker sedative than clozapine, and vice versa. The plausibility of this hypothesis was demonstrated. Partly also on the basis of earlier research, we concluded that the biochemical action of a neuroleptic is a more faithful predictor of its therapeutic action profile than the chemical structure.Keywords
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