In vitro extrastriatal and striatal D-2 dopamine receptor blockade by amisulpride in schizophrenia

Amisulpride, a substituted benzamide with high affinity for dopamine D-2 an d D-3 receptors only, has been reported to have therapeutic effects on both negative and positive schizophrenic symptoms, although at distinct dose ra nges (50-300 mg/day vs. 400-1,200 mg/day). The purpose of this study was to investigate the binding of amisulpride to extrastriatal (i.e., thalamus an d temporal cortex) and striatal D-2 dopamine receptors with respect to plas ma amisulpride determinations. Ten patients with schizophrenia treated with amisulpride over a wide range of doses (25-1,200 mg/day) were studied. Pos itron emission tomography images were acquired by using Br-76-FLB-457, a hi ghly specific antagonist of the D-2 and D-3 dopamine receptors. Binding ind exes (BI) in the regions studied were estimated with reference to values fr om six healthy subjects. A curvilinear relationship was demonstrated betwee n plasma concentration of amisulpride and the BI in extrastriatal regions. The BI also varied as a function of plasma concentration in striatum. Furth ermore, the data provide evidence for different binding profiles: low plasm a concentrations (28-92 ng/mL) induced marked extrastriatal binding and low striatal binding, whereas higher plasma concentrations (>153 ng/ mL) induc ed marked binding both in extrastriatal and striatal regions. Dose-dependen t differential binding profiles of amisulpride to D-2 receptors in extrastr iatal and striatal regions were demonstrated, and two therapeutic ranges of plasma concentrations for negative and positive schizophrenic symptoms, re spectively, are suggested.