In vivo occupancy of striatal and temporal cortical D-2/D-3 dopamine receptors by typical antipsychotic drugs - [I-123]-epidepride single photon emission tomography (SPET) study

Background The dopamine hypothesis proposes that antipsychotic drugs act pr imarily through limbic cortical D-2/D-2-like dopamine receptor blockade. Aim To evaluate this hypothesis with the D-2/D-3-selective SPET probe [I-12 3]-epidepride. Method [I-123]-epidepride SPET scans were performed on 12 patients with sch izophrenia treated with antipsychotics and 11 age- matched healthy controls . [I-123]-epidepride 'specific binding' to D-2/D-3 dopamine receptors was e stimated, and relative percentage D-2/D-3 receptor occupancy by typical ant ipsychotic drugs determined. Results Mean (s.d.) daily dose was 669.12 (516.8) mg chlorpromazine equival ents. Mean percentage D-2/D-3, receptor occupancy was 81.6 (8.1) and 73.2 ( 13.9) in the temporal cortex and striatum respectively. Conclusions Typical antipsychotic drug treatment is associated with substan tial temporal cortical D-2/D-3 receptor occupancy. The relationship between this and efficacy is poor in patients with treatment-resistant schizophren ia. Declaration of interest L.P. was supported by a Medical Research Council Cl inician Scientist Fellowship. V.B. was supported by a research grant from E li Lilly Pharmaceuticals.