Inhibition of Prolactin Secretion by Ergolines

Peptide-containing ergot alkaloids and synthetic ergoline derivatives were administered to reserpine-treated male rats in order to evaluate their prolactin-inhibiting properties. Each compound was administered ip at a standard 50 ¼g/kg dose. The 9,10-dihydrogenated ergots, dihydroergocornine, and dihydroergocryptine were able to inhibit prolactin to the same degree as ergocornine and ergocryptine. This is significant because the 9,10-dihydrogenation process removes the toxic vasoconstrictive properties from the molecule and allows the prolactin-inhibiting ability to remain intact. In addition, dose-response studies show that minute amounts of an ergot can cause a significant reduction in prolactin secretion. The failure of ergocorninine to inhibit prolactin secretion demonstrates that the stereochemical configuration of the molecule at the 8 position is important for prolactin-inhibiting ability. Interestingly, a number of simple ergot molecules lacking the peptide side chain are able to inhibit prolactin secretion. Substitution at the 1 or 2 position as well as hydrogenation of the indole reduces the prolactin-inhibiting activity. The most active compound is D6-methyl-8βergolineacetonitrile. The high prolactin-inhibiting potency of these compounds suggests that they are able to mimic prolactin-inhibiting factor (PIF). (Endocrinology94: 1171, 1974)