In vivo binding of [11C]nemonapride to sigma receptors in the cortex and cerebellum.
Radiolabeled nemonapride (NEM, YM-09151-2) is widely used as a representative dopamine D2-like receptor ligand in pharmacological and neurological studies, and 11C-labeled analog ([11C]NEM) has been developed for positron emission tomography (PET) studies. The aim of this study was to evaluate whether [11C]NEM binds in vivo to sigma receptors. [11C]NEM and one of six dopamine D2-like receptor ligands or seven sigma receptor ligands were co-injected into mice, and the regional brain uptake of [11C]NEM was measured by a tissue dissection method. The striatal uptake of [11C]NEM was reduced by D2-like receptor ligands, NEM, haloperidol, (+)-butaclamol, raclopride, and sulpiride, but not by a D4 receptor ligand clozapine. In the cortex and cerebellum the uptake was also reduced by D2-like receptor ligands with affinity for sigma receptors, but not by raclopride. Although none of seven sigma receptor ligands, SA6298, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]ethylamine hydrochloride (NE-100), (+)-pentazocine, R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2-aminopropane hydrochloride ([-]-PPAP), (-)-pentazocine, R(+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ([+]-3-PPP), and (+)-N-allylnormetazocine hydrochloride ([+]-SKF 10047), blocked the striatal uptake, five of them with relatively higher affinity significantly reduced the [11C]NEM uptake by the cortex, and four of them reduced that by the cerebellum. We concluded that [11C]NEM binds in vivo not only to dopamine D2-like receptors in the striatum but also to sigma receptors in other regions such as cortex and cerebellum.
Ishiwata
K
K
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi, Japan. ishiwata@pet.tmig.or.jp
Senda
M
M
D000818:Animals; D001549:Benzamides / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists / Q000493:pharmacokinetics*; D007700:Kinetics; D051379:Mice; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D017480:Receptors, sigma / Q000032:analysis / Q000378:metabolism*
D001549:Benzamides; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; C030265:nemonapride