Clozapine versus perphenazine: the value of the biochemical mode of action of neuroleptics in predicting their therapeutic activity.
The chemical structure of a neuroleptic does not relaibly 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 anc 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.
D000328:Adult; D003024:Clozapine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003984:Dibenzazepines / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008875:Middle Aged; D019965:Neurocognitive Disorders / Q000188:drug therapy; D009638:Norepinephrine / Q000378:metabolism; D010546:Perphenazine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D010919:Placebos; D011618:Psychotic Disorders / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000187:drug effects
D003984:Dibenzazepines; D006993:Hypnotics and Sedatives; D010919:Placebos; D011954:Receptors, Dopamine; D010546:Perphenazine; D003024:Clozapine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid