Multiple [3H]-nemonapride binding sites in calf brain.
[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.
Helmeste
D M
DM
Department of Psychiatry and Human Behavior, University of California, Irvine 92697-1681, USA.
Tang
S W
SW
Li
M
M
Fang
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism; D001549:Benzamides / Q000378:metabolism*; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002417:Cattle; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D004146:Dioxanes / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism; D018492:Dopamine Antagonists / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D006220:Haloperidol / Q000378:metabolism; D066298:In Vitro Techniques; D007553:Isotope Labeling; D009292:Narcotic Antagonists / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism; D011437:Propylamines / Q000378:metabolism; D011759:Pyrrolidines / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D001549:Benzamides; D004146:Dioxanes; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D006146:Guanidines; D009292:Narcotic Antagonists; D010880:Piperidines; D011437:Propylamines; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D017480:Receptors, sigma; D014316:Tritium; C068473:N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D013469:Sulpiride; C026539:preclamol; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D006220:Haloperidol; C050232:1,3-ditolylguanidine; C030265:nemonapride; D010423:Pentazocine