Abstract
[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.
MeSH terms
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Adrenergic alpha-Antagonists / metabolism
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Animals
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Anticonvulsants / metabolism
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Benzamides / metabolism*
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Binding, Competitive / drug effects
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Brain / metabolism*
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Cattle
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Cerebellum / metabolism
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Cerebral Cortex / metabolism
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Corpus Striatum / metabolism
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Dioxanes / metabolism
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Dopamine Agonists / metabolism
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Dopamine Antagonists / metabolism*
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Guanidines / metabolism
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Haloperidol / metabolism
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In Vitro Techniques
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Isotope Labeling
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Narcotic Antagonists / pharmacology
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Pentazocine / pharmacology
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Piperidines / metabolism
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Propylamines / metabolism
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Pyrrolidines / metabolism
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Receptors, Dopamine D2 / drug effects
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Receptors, Dopamine D2 / metabolism
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Receptors, sigma / drug effects
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Receptors, sigma / metabolism
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Sulpiride / pharmacology
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Tritium
Substances
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Adrenergic alpha-Antagonists
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Anticonvulsants
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Benzamides
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Dioxanes
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Dopamine Agonists
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Dopamine Antagonists
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Guanidines
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Narcotic Antagonists
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Piperidines
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Propylamines
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Pyrrolidines
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Receptors, Dopamine D2
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Receptors, sigma
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Tritium
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N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane
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3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
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Sulpiride
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preclamol
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(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
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Haloperidol
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1,3-ditolylguanidine
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nemonapride
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Pentazocine