Dopamine Antagonism and Antischizophrenic Potency of Neuroleptic Drugs

Abstract

IT has been argued^1–4 that ability to block central dopamine receptors is related to the therapeutic potency of neuroleptic drugs in schizophrenia. Two lines of evidence favour this hypothesis. First, dopamine antagonism probably underlies the “extrapyramidal” or Parkinsonian side effects of neuroleptic drugs⁵, and such side effects are a frequent concomitant of the therapeutic effects of these drugs when used in patients suffering from schizophrenia^6–8. Second, the psychosis provoked by amphetamine administration closely resembles paranoid schizophrenia^9–11, and biochemical, pharmacological and histochemical evidence^12–16 suggests that amphetamines act in the CNS at least partly by causing dopamine release. Moreover, (+) and (−) amphetamine are approximately equipotent in eliciting psychotic symptoms¹⁷, and this potency ratio would be expected if the psychological phenomena were dependent upon an action upon central dopaminergic, rather than noradrenergic, mechanisms. The central actions of the amphetamines are reversed by phenothiazine administration in animal experiments^2,15 and in man¹⁸.