Biochemical research into psychosis

Abstract

A strategy is presented for biological psychosis research with neuroleptics acting as a point of crystallisation like antidepressants do in biological depression research. The neuroleptics chlorpromazine, haloperidol and oxypertine were studied, and it was found that they influence central catecholamine (CA) metabolism in man. An increased central dopamine (DA) turnover was found to occur in psychotic disorders, mostly in the form of motor agitation. As the first of a planned series of studies, chlorpromazine with presumed ability to reduce both DA-ergic and noradrenaline (NA)-ergic transmission and oxypertine as a more selective blocker of NA-ergic transmission were selected for comparison. The overall therapeutic effect of oxypertine was inferior to that of chlorpromazine, whereas oxypertine proved more effective in cases where loss of initiative was predominant. On the other hand, chlorpromazine exerted a more marked influence on extrapyramidal motor functions than oxypertine. In chronic psychotic disorders with inertia, oxypertine thus seems to be a neuroleptic which is strong enough to prevent exacerbation of delusions and hallucinations while at the same time increasing the level of motivation. These findings were in accordance with our predictions. The comparative study is illustrative of the practical significance of the research approach in this study: The biochemical action profile of a neuroleptic seems to be a more reliable indicator of its clinical action than does its chemical structure.