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

James M Stone, John M Davis, Stefan Leucht, Lyn S Pilowsky

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Abstract

Subject numbers in neuroreceptor imaging studies of antipsychotic treatment in schizophrenia are generally insufficient to directly test the relationship of regional D(2)/D(3) and 5HT(2A) receptor binding to clinical efficacy. We selected positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies of antipsychotic dose vs occupancy at both temporal cortex and striatal D(2)/D(3) receptors. We selected corresponding SPECT and PET studies of 5HT(2A) 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 optimum effective antipsychotic dose with the dose inducing maximal occupancy of D(2)/D(3) receptors in striatum and in temporal cortex as well as at 5HT(2A) receptors. Both first- and second-generation antipsychotic (FGA, SGA) drugs produced high temporal cortex D(2)/D(3) occupancy. Only FGA produced high striatal D(2)/D(3) receptor occupancy. The clinically effective dose showed correlation with doses inducing maximal dopamine D(2)/D(3) receptor occupancy both in striatum and in temporal cortex, the strongest correlation being with temporal cortex binding. Extrapyramidal side effects (EPSE) were primarily related to striatal D(2)/D(3) receptor occupancy. There was no correlation between 5HT(2A) occupancy and clinically effective dose. We conclude that cortical dopamine D(2)/D(3) receptor occupancy is involved in antipsychotic efficacy, with striatal D(2)/D(3) occupancy having a likely therapeutic role while also inducing EPSE. We found no evidence for 5HT(2A) blockade involvement in antipsychotic action, although we cannot exclude this possibility.
Original languageEnglish
Article numberN/A
Pages (from-to)789-797
Number of pages9
JournalSchizophrenia Bulletin
Volume35
Issue number4
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Antipsychotic Agents
  • Cerebral Cortex
  • Humans
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Randomized Controlled Trials as Topic
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Receptors, Serotonin
  • Schizophrenia
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome

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