Dopaminergic mechanisms in schizophrenia: The antipsychotic effect and the disease process

Abstract

A controlled trial of the isomers of flupenthixol in acute schizophrenia demonstrated that only the α-isomer possesses antipsychotic activity. The result is consistent with the hypothesis that dopamine receptor blockade is the only requirement for therapeutic activity. However, the onset of the therapeutic effect was slow, and delayed by at least two weeks by comparison with the establishment of receptor blockade as indicated by increased prolactin secretion. In post-mortem brain tissue dopamine turnover was found not to be increased in patients with schizophrenia. However, receptor density, assessed by the spiroperidol-binding technique, was significantly increased, and this increase was present in five patients who apparently had not received neuroleptic medication for at least one year before death.