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.
Raclopride and remoxipride, which are reported to be selective dopamine-D2 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 levels of alpha-melanocyte-stimulating hormone (alpha-MSH). These results suggest that although raclopride and remoxipride are both classified as D2 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.
Eaton
M J
MJ
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Tian
Y
Y
Lookingland
K J
KJ
Moore
K E
KE
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008032:Limbic System / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D020891:Raclopride; D011863:Radioimmunoassay; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000502:physiology; D017330:Remoxipride / Q000494:pharmacology*; D012457:Salicylamides / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects; D013997:Time Factors; D000521:alpha-MSH / Q000097:blood / Q000378:metabolism*
D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D017330:Remoxipride; D020891:Raclopride; D000521:alpha-MSH; D011388:Prolactin