The semisynthetic ergoline dopamine agonist pergolide has demonstrated
activity at pre- and postsynaptic dopamine D-2 receptors in in vitro
and in vivo animal studies. However, unlike other dopamine agonists su
ch as bromocriptine, pergolide also has agonist activity at dopamine D
-1 receptors. Certain other pharmacological effects of pergolide, such
as reduction of dopamine turnover and effects on free radical scaveng
ing enzymes, may be relevant in the early treatment of Parkinson's dis
ease but this has not been conclusively determined. Short and long ter
m noncomparative studies show that pergolide is an effective adjunct t
o levodopa therapy in patients with advancing Parkinson's disease, red
ucing the adverse effects of long term levodopa monotherapy and often
enabling a reduction in levodopa dosage. In placebo comparisons pergol
ide was generally more effective than placebo and was associated with
benefits similar to those seen in noncomparative studies. Longitudinal
comparisons in individual patients indicate that the antiparkinsonian
efficacy of pergolide is similar to that of mesulergine, lergotrile a
nd lisuride, and may be superior to that of bromocriptine. Controlled
comparisons with bromocriptine tend to support this latter finding. St
udies evaluating the efficacy of pergolide as monotherapy early in the
course of Parkinson's disease have shown the drug to be effective, bu
t opinion is divided as to the value of early treatment with dopamine
agonists (as opposed to levodopa monotherapy). Thus, pergolide is an e
ffective adjunct to levodopa therapy in patients with advanced Parkins
on's disease and may have a role in the treatment of early disease if
its postulated beneficial effects on disease progression are proven.