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Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition, compulsive turning, and stereotypic behavior.

Four pergolide metabolites and bromocriptine (CAS 25614-03-3) were compared to pergolide (8 beta-[(methylthio) methyl]-6-propyl-ergoline, CAS 66104-22-1) using three in vivo animal models of activity at dopamine receptors. The results obtained from these studies of prolactin inhibition, induction of compulsive turning, and stimulation of stereotypic behavior, were very consistent. Two of the metabolites, despropyl pergolide and despropyl pergolide sulfoxide, were devoid of dopamine-like effects in any of the models. Pergolide sulfone and pergolide sulfoxide, however, were found to be potent dopamine agonists, similar in activity to pergolide itself. Dopamine D2 receptors (and probably D1 receptors also) appear to be involved in the activities of these compounds. The compounds were active by both oral and i.p. routes of administration. Bromocriptine, while possessing some dopamine agonist activity at higher doses in some of these animal models, was much less potent (1/200 to 1/20) than either pergolide or its two dopaminergic metabolites.