Search

Background Selective action at limbic cortical dopamine D2-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. Aims To test the hypothesis that quetiapine has ‘limbic selective’ D2/D3 receptor occupancy in vivo. Method The high-affinity D2/D3 ligand [123I]-epidepride and single photon emission tomography were used to estimate D2/D3 specific binding and an index of relative percentage D2/D3 occupancy in striatal and temporal cortical regions for quetiapine-treated patients (n=6). Quetiapine-, and previously studied typical-antipsychotic- and clozapine-treated patients were compared. Results Mean (s.d.) relative percentage D2/D3 receptor occupancy by quetiapine was 32.0% (14.6) in striatum and 60.1% (17.2) in temporal cortex (mean daily dose 450 mg: range 300-700 mg/day). Quetiapine treatment resulted in limbic selective D2/D3 blockade similar to clozapine and significantly higher than typical antipsychotics. Conclusions Preliminary data suggest that limbic selective D2/D3 receptor blockade is important for atypical drug action. [ABSTRACT FROM AUTHOR]

Imaging receptors using radioactive ligands has allowed direct determination of the sites of action of antipsychotic drugs. Initial studies relating antipsychotic drug efficacy to action at striatal dopamine D2-like receptors have recently been undermined. Developments in imaging extrastriatal dopamine D2-like receptors suggest rather that antagonism of these receptors in the temporal cortex is the common site of action for antipsychotic drugs, with occupancy at striatal receptors relating more closely to extrapyramidal side effects. Further work into dopamine receptor subtypes and other receptor groups such as serotonin and GABA neurotransmitters awaits the development of suitable probes, but there are some initial finding. Again a main site of antipsychotic drug action is at cortical levels with high degrees of cortical D1 and 5HT2a receptor occupancy attained particularly by atypical antipsychotic drugs.