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

[H-3]-Nemonapride has been the ligand of choice to label D-4 dopamine receptors, Its specificity was questioned when it was discovered that sigma (sigma) sites were also labeled by [H-3]-nemonapride. To further characterize the binding of [H-3]-nemonapride, three areas of calf brain (striatum, frontal cortex and cerebellum) were examined. In all three areas, [H-3]-nemonapride labeled multiple sites. Dopaminergic and sigma sites were the most prominent. The sigma binding profile was sigma-1 like with a K-i 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 [H-3]-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, [H-3]-nemonapride has no selectivity for dopamine receptors unless stringent experimental conditions are met.