title: The putatively selective dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 stimulate prolactin release in rats.
abstract: The 2-aminotetralin derivatives cis-(+)-(1S,2R)-5-methoxyl-1-methyl-2-(n-propylamino)tetralin, (+)-AJ 76, and cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin, (+)-UH 232, are novel centrally acting stimulants with a putative action as selective dopamine (DA) autoreceptor antagonists. In the present study these compounds were evaluated with respect to their effects on prolactin release in male rats. Both (+)enantiomers caused a pronounced increase in plasma prolactin levels in previously untreated animals. The effects of (+)-AJ 76 and (+)-UH 232 were virtually similar, except for a higher initial increase after the latter compound. In agreement with earlier reports, the reserpine-induced elevation of plasma levels of prolactin was strongly suppressed by the DA autoreceptor agonist B-HT 920. This effect of B-HT 920 was completely blocked by (+)-AJ 76 and by (+)-UH 232, indicating that both (+)enantiomers antagonize lactotroph DA receptors. The present findings support the notion that lactotroph DA receptors resemble DA autoreceptors rather than postsynaptic DA receptors. A possible difference between the auto-/lactotroph vs. postsynaptic DA receptors with respect to both the responsiveness to agonists and to the affinity of pure antagonists is discussed.
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001381:Azepines; D009281:Naphthalenes; D011954:Receptors, Dopamine; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C024763:talipexole; C051171:5-methoxy-1-methyl-2-(n-propylamino)tetralin; D012110:Reserpine; D011388:Prolactin; C045971:UH 232