Antipsychotic drug mechanisms and neurotransmitter systems in schizophrenia

The dopamine hypothesis of schizophrenia has been central to the understanding of the mechanism of action of the antipsychotic drugs. Certainly the close correlation between drug dosage and affinity for D2 dopamine receptors indicates the importance of these receptors in the antipsychotic response, although D2 antagonism can also induce acute extrapyramidal side effects. The antipsychotic drugs also act at other neurotransmitter receptors, and these actions contribute to the unwanted side effects of treatment. The use of selective D2 antagonists can diminish such effects, although effects at other receptors are reported to be of value in minimizing extrapyramidal syndromes as well as in enhancing response either directly or by diminishing negative symptoms. The present understanding of these receptor mechanisms is reviewed.