Discrepancies in apparent dopamine D2 receptor occupancy between 3H-raclopride and 3H-N-methylspiperone

Competitive inhibition of H-3-raclopride (RAC) and H-3-N-methylspiperone (NMSP) binding against haloperidol, raclopride and NMSP was measured in the mouse striatum. H-3-RAC binding was more sensitive to competitive inhibition by all three compounds compared with H-3-NMSP. For example, 0.3 mg/kg of haloperidol resulted in 95% inhibition of H-3-RAC binding, however only 60% of inhibition of H-3-NMSP binding was found at the same dose of haloperidol. The cross-inhibition experiments using nonradioactive RAC or NMSP as competitors indicated different binding sites for H-3-RAC and H-3-NMSP in mouse striatum. Specifically, about 40% of H-3-NMSP binding was not displaced by treatment with a very high dose of raclopride (3 mg/kg). The time course of inhibition of the specific binding of H-3-RAC and H-3-NMSP were measured following i.p. injection of 0.5 mg/kg of haloperidol. No significant differences in the kinetics of haloperidol inhibition were observed between two radioligands.