Striatal and extra-striatal D2/D3 dopamine receptor occupancy by quetiapine in vivo -: [123I]-epidepride single photon emission tomography (SPET) study

Background Selective action at limbic cortical dopamine D-2-like receptors could mediate atypical antipsychotic efficacy with few extrapyramidal side-effects. Aims To test-the hypothesis that quetiapine has 'limbic selective' D-2/D-3 receptor occupancy in vivo. Method The high-affinity D-2/D-3 ligand [I-123]-epidepride and single photon emission tomography were used to estimate D-2/D-3 specific binding and an index of relative percentage D-2/D-3 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 D-2/D-3 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 D-2/D-3 blockade similar to clozapine and significantly higher than typical antipsychotics. Conclusions Preliminary data suggest that limbic selective D-2/D-3 receptor blockade is important for atypical drug action. Declaration of interest C.M.E.S. and H.M.J. were supported by research grants from AstraZeneca, V.B. by a research grant from Eli Lilly and R.S.M. by a UK Medical Research Council (MRC) Senior Clinical Research Fellowship Award. LS.P. is a UK MRC Senior Clinical Research Fellow.