Multiple [3H]-nemonapride binding sites in calf brain

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1997-07, Vol.356 (1), p.17-21
• Main Authors: Helmeste, D M, Tang, S W, Li, M, Fang, H
• Format: Article
• Language: English
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Adrenergic alpha-Antagonists - metabolism; Animals; Anticonvulsants - metabolism; Benzamides - metabolism; Binding, Competitive - drug effects; Brain - metabolism; Cattle; Cerebellum - metabolism; Cerebral Cortex - metabolism; Corpus Striatum - metabolism; Dioxanes - metabolism; Dopamine Agonists - metabolism; Dopamine Antagonists - metabolism; Guanidines - metabolism; Haloperidol - metabolism; In Vitro Techniques; Isotope Labeling; Narcotic Antagonists - pharmacology; Pentazocine - pharmacology; Piperidines - metabolism; Propylamines - metabolism; Pyrrolidines - metabolism; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, sigma - drug effects; Receptors, sigma - metabolism; Sulpiride - pharmacology; Tritium
• ISSN: 0028-1298
• DOI: 10.1007/PL00005023

[3H]-Nemonapride has been the ligand of choice to label D4 dopamine receptors. Its specificity was questioned when it was discovered that sigma (sigma) sites were also labeled by [3H]-nemonapride. To further characterize the binding of [3H]-nemonapride, three areas of calf brain (striatum, frontal cortex and cerebellum) were examined. In all three areas, [3H]-nemonapride labeled multiple sites. Dopaminergic and sigma sites were the most prominent. The sigma binding profile was sigma-1 like with a Ki binding profile as follows (in order of decreasing potency): haloperidol, PPAP, pentazocine, DTG, U-50488, R(+)-3-PPP. Experiments using sulpiride and pentazocine to block striatal dopaminergic and sigma sites, respectively, revealed additional, not previously characterized binding sites for [3H]-nemonapride. One component which was present in striatum but not in frontal cortex or cerebellum, had affinity for some neuroleptics and WB-4101, but not for typical serotonergic agents. Thus, [3H]-nemonapride has no selectivity for dopamine receptors unless stringent experimental conditions are met.