Cortical dopamine d2/d3 receptors are a common site of action for antipsychotic drugs—An original patient data meta-analysis of the spect and pet in vivo receptor imaging literature

Subject numbers inneuroreceptor imagingstudiesofantipsy-chotic treatment in schizophrenia are generally insufficient to directly test the relationship of regional D2/D3 and 5HT2A receptor binding to clinical efficacy. We selected positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies of antipsy-chotic dose vs occupancy at both temporal cortex and striatal D2/D3 receptors. We selected corresponding SPECT and PET studies of 5HT2A receptor occupancy. We also selected randomized double-blind clinical trials of antipsychotics, where patients were treated with randomly assigned fixed doses. For each antipsychotic drug, we compared the opti-mum effective antipsychotic dose with the dose inducing maximal occupancy of D2/D3 receptors in striatum and in temporal cortex as well as at 5HT2A receptors. Both first-and second-generation antipsychotic (FGA, SGA) drugs produced high temporal cortex D2/D3 occupancy. Only FGA produced high striatal D2/D3 receptor occupancy. The clinically effective dose showed correlation with doses inducing maximal dopamine D2/D3 receptor occupancy both in striatum and in temporal cortex, the strongest corre-lation being with temporal cortex binding. Extrapyramidal side effects (EPSE) were primarily related to striatal D2/D3 receptor occupancy. There was no correlation between 5HT2A occupancy and clinically effective dose. We conclude that cortical dopamine D2/D3 receptor occupancy is involved in antipsychotic efficacy, with striatal D2/D3 occupancy hav-ing a likely therapeutic role while also inducing EPSE. We found no evidence for 5HT2A blockade involvement in anti-psychotic action, although we cannot exclude this possibility. Key words: schizophrenia/antipsychotic/efficacy/limbic selectivity/EPSE/SPEC