CHARACTERIZATION OF [H-3] NEMONAPRIDE BINDING TO MOUSE-BRAIN DOPAMINED-2 RECEPTORS ASSESSED IN-VIVO AND EX-VIVO FOR METABOLIC MODELING IN PET STUDIES

We characterized [H-3]nemonapride ([H-3]NEM, [H-3]YM-09151-2) binding to dopamine D-2 receptors. In mice given [H-3]NEM with and without sul piride, the in vivo specific binding of the [H-3]NEM to the D-2 recept ors in the striatum was assessed: SBin vivo-1, striatal uptake minus c erebellar uptake; and SBinvivo-2, uptake in the control mice minus upt ake in the sulpiride-treated mice. Tissue homogenates were divided int o cytosol and the membrane binding fraction (MB). When the MB was incu bated in vitro with sulpiride, the dissociated and nondissociated frac tions were defined as the ex vivospecific binding (SBex vivo) and the ex vivo nonspecific binding (NBex vivo), respectively. HPLC revealed t hat most of the radioactivity in the MB was [H-3]NEM, whereas metaboli tes were found in the cytosol. In the striatum, the SBex vivo increase d with time (50% of the total tissue uptake at 60 min), and was equiva lent to the SBin vivo-2. The SBin vivo-1 was comparable to the MB. In the cerebral cortex and cerebellum, the SBex vivo decreased with time and the SBex vivo/free [H-3]NEM ratios were smaller than those in the striatum.