The Inhibitory Effect of an Ergoline Derivative (Lergotrile, Compound 83636) on Prolactin Secretion in Man

Abstract

Compound 83636 (lergotrile), an ergoline derivative, inhibits prolactin release in vitro and in vivo in animals. Studies were designed to evaluate its clinical pharmacologic effects in man. Its chronic administration (2 mg 3 times daily) to normal volunteers and patients results in a decrease in serum prolactin levels. Pretreatment of subjects with single doses of 2, 4, or 6 mg of Compound 83636 delayed the onset of perphenazine-induced elevation of serum prolactin in a dose-dependent fashion. Administration of Compound 83636 (4 or 6 mg) 1 hr after perphenazine administration resulted in a decrease in the elevated serum prolactin levels towards baseline within 15 to 30 min. One week's chronic treatment with Compound 83636 (2 mg 3 times daily) attenuated the expected perphenazineinduced rise in serum prolactin. Compound 83636 appeared to have no significant effect on growth hormone, T3, T4, LH or FSH when compared to determinations made during a placebo control period. It appears that Compound 83636 is a specific inhibitor of prolactin release and may be beneficial in disease states in which lowering serum prolactin is important.