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.