Dopamine and antipsychotic drug action revisited

[...]clozapine, a therapeutically superior antipsychotic drug without extrapyramidal side-effects (and modest affinity for D2 receptors in vitro) had consistently low levels of D2 receptor blockade (ranging from 20% to 60%) in association with excellent clinical response, even in patients previously poorly responsive to standard or high-dosage typical antipsychotic drug therapy (Pilowsky et al, 1992). Consideration of the D2 receptor affinity and occupancy data relating to typical and atypical antipsychotic drugs led Kapur & Seeman (2001) to conclude that owing to low affinity for the D2 receptor (driven, as these authors see it, by fast dissociation ‘off’ the receptor) clozapine and quetiapine exhibit transiently high D2 receptor occupancy (not exceeding the threshold required to induce adverse movement or hormonal side-effects), which declines to very low levels over a 24 h period. The availability of high- and low-affinity D2/D3 receptor antagonist antipsychotic drugs offers clinicians much choice, and the above data provide a rational evidence base for prescribing, tailored as far as possible to individual patient responses. L.S.P. is a UK Medical Research Council Senior Clinical Fellow and has received research grants from Astrazeneca, Novartis, Janssen and Sanofi-Synthelabo, and honoraria for lectures and consultancies to GlaxoSmith Kline, Astrazeneca, Novartis, Pfizer and Janssen.