Pergolide inhibition

A 5-(methylthio)methyl-substituted derivative (cis-28) of ( + )-3-PPP has been reported [91]. The background to the study was the structural similarity between pergolide (29) and (cis-28). However, the biological testing of (cis-28) showed that it is inactive in vivo (GBL model), while an in vitro assay (inhibition of tyrosine hydroxylation) showed (cis-28) to be equipotent to racemic 3-PPP itself. These results indicate that the steric bulk in (cis-28) is not compatible with potent DA receptor interaction. However, since compound (cis-28) was not resolved, there is a possibility that one or both of the enantiomers of (cis-28) might have antagonistic properties [89]. 

Figure 8. The inhibition of electrically evoked 3H-dopamine release by pergolide, and its dependence on frequency of stimulation. (Reproduced with permission from Ref. 122. Copyright 1982, Pergamon Press, Ltd.)...

F. Prolactin-Inhibiting Hormone (PIH, Dopamine) Dopamine is the physiologic inhibitor of prolactin release. Because of its peripheral effects and the need for parenteral administration, dopamine is not useful in the control of hyperprolactinemia, but bromocriptine and other orally active ergot derivatives (eg, cabergoline. pergolide) are effective in reducing prolactin secretion from the normal gland as well as from pituitary tumors. 

Bromocriptine, pergolide, cabergoline Inhibit prolactin release Stop lactation inhibit growth of pituitary tumors Ergot alkaloid derivatives with potent dopamine agonist activity... 

Clemens, J.A., Okimura, T. and Smalstig, E.B. (1993) Dopamine agonist activities of pergolide, its metabolites, and bromocriptine as measured by prolactin inhibition. 

---