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Striatal and extra-striatal D₂/D₃ dopamine receptor occupancy by quetiapine in vivo

[¹²³I]-epidepride single photon emission tomography(SPET) study

Institute of Psychiatry, London

R. S. MULLIGAN, Msc, D. VISVIKIS, PhD and P. J. ELL, FRCP

Institute of Nuclear Medicine, UCL Medical School, Middlesex Hospital, London

P. D. ACTON, PhD

Department of Radiology, University of Pennsylvania

Correspondence: C. M. E. Stephenson, c/o L. S. Pilowsky, Department of Psychological Medicine, Section of Neurochemical Imaging, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

Declaration of interest C.M.E.S. and H.M.J. were supported by research grants from Astra Zeneca, 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. L.S.P. is a UK MRC Senior Clinical Research Fellow.

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.

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