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

J Neural Transm (Vienna). 1999;106(11-12):1099-104. doi: 10.1007/s007020050226.

Abstract

Competitive inhibition of 3H-raclopride (RAC) and 3H-N-methylspiperone (NMSP) binding against haloperidol, raclopride and NMSP was measured in the mouse striatum. 3H-RAC binding was more sensitive to competitive inhibition by all three compounds compared with 3H-NMSP. For example, 0.3 mg/kg of haloperidol resulted in 95% inhibition of 3H-RAC binding, however only 60% of inhibition of 3H-NMSP binding was found at the same dose of haloperidol. The cross-inhibition experiments using non-radioactive RAC or NMSP as competitors indicated different binding sites for 3H-RAC and 3H-NMSP in mouse striatum. Specifically, about 40% of 3H-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 3H-RAC and 3H-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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • Brain Chemistry / drug effects
  • Male
  • Mice
  • Raclopride / metabolism*
  • Raclopride / pharmacology*
  • Radioligand Assay
  • Receptors, Dopamine D2 / metabolism*
  • Spiperone / analogs & derivatives*
  • Spiperone / metabolism
  • Spiperone / pharmacology
  • Tritium

Substances

  • Receptors, Dopamine D2
  • Tritium
  • Raclopride
  • Spiperone
  • 3-N-methylspiperone