The Significance of Dopamine for the Mode of Action of Neuroleptics and the Pathogenesis of Schizophrenia

Animal experiments have demonstrated the likehood that all known neuroleptics inhibit transmission in central CA-ergic systems, regardless of their chemical structure and via different mechanisms. For clinical psychiatry this fact prompts a number of questions: (1) is this phenomenon also to be found in human individuals; (2) if so, is it of importance for the clinical (side) effects of neuroleptics; (3) do patients with (schizophrenic) psychoses show signs of central CA-ergic hyperactivity? This article presents a survey of clinical research focused on these questions which, for the sake of brevity, is confined to DA metabolism. The available data indicate the plausibility of a correlation between inhibition of DA-ergic transmission on the one hand, and on the other hand the therapeutic effects of neuroleptics and the occurrence of hypokinetic-rigid symptoms. The hypothesis that DA-ergic hyperactivity is an important pathogenetic mechanism in schizophrenic psychoses can be based only on indirect arguments; direct studies of the DA metabolism have so far failed to reveal supporting evidence. The possible causes of this failure are discussed.