Discrepancies in apparent dopamine D2 receptor occupancy between 3H-raclopride and 3H-N-methylspiperone.
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.
Inoue
O
O
Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Suita, Japan.
Kobayashi
K
K
Hosoi
R
R
Yamaguchi
M
M
Gee
A
A
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D020891:Raclopride / Q000378:metabolism* / Q000494:pharmacology*; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013134:Spiperone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
D017448:Receptors, Dopamine D2; D014316:Tritium; D020891:Raclopride; D013134:Spiperone; C039167:3-N-methylspiperone