Dopamine agonistic potency of two novel prolactin release-inhibiting ergolines.
Two novel 8 alpha-amino ergolines (CH 29-717 and CU 32-085) have been shown to inhibit secretion of prolactin in rats in vivo. However, when tested for dopaminomimetic potency on pituitary cell culture preparations in vitro, CH 29-717 inhibited prolactin release with an IC50 = 4 X 10(-9) M. In the same model the 1-methyl-derivative CU 32-085 was only weakly active even at high concentrations. When both compounds were incubated together, CU 32-085 displayed an inhibitory effect on the prolactin release restriction caused by CH 29-717. The activities were not time-dependent since similar results were obtained with incubation for 3 or 24 h. These results support the hypothesis that the 1-methyl ergoline derivative CU 32-085 is a partial agonist and becomes fully active in vivo only after metabolic conversion.
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004873:Ergolines; C018794:CH 29717; D011388:Prolactin; C031649:mesulergine; D004298:Dopamine