Comparison of the effects of remoxipride and raclopride on nigrostriatal and mesolimbic dopaminergic neuronal activity and on the secretion of prolactin and alpha-melanocyte-stimulating hormone
Eaton, M.J.; Tian, Y.; Lookingland, K.J.; Moore, K.E.
Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology 7(3): 205-211
1992
ISSN/ISBN: 0893-133X PMID: 1326981 Document Number: 397297
Raclopride and remoxipride which are reported to be selective dopamine-D-2 antagonists, are currently under clinical investigation as antipsychotic drugs. The present study compared the relative abilities of these two drugs to alter the activity of nigrostriatal and mesolimbic dopaminergic neurons, and plasma levels of hormones originating from the anterior and intermediate lobes of the pituitary in male rats. Although raclopride was consistently more potent than remoxipride, both drugs produced dose- and time-related increases in concentrations of 3,4-dihydroxyphenylacetic acid in the striatum and nucleus accumbens, which contain terminals of nigrostriatal and mesolimbic dopaminergic neurons, respectively. Both drugs also caused significant dose- and time-related increases in plasma levels of prolactin, but only raclopride increased plasma levles of alpha-melanocyte-stimulating hormone (alpha-MSH). These results suggest that although raclopride and remoxipride are both classified as D-2 receptor antagonists they can be distinguished from one another by their relative ability to block the inhibitory dopaminergic control of alpha-MSH from melanotrophs in the intermediate lobe of the rat pituitary.