PERGOLIDE SCAVENGES BOTH HYDROXYL AND NITRIC-OXIDE FREE-RADICALS IN-VITRO AND INHIBITS LIPID-PEROXIDATION IN DIFFERENT REGIONS OF THE RAT-BRAIN

The free radical hypothesis for the pathogenesis and/or progression of Parkinson's disease (PD) has gained wide acceptance in recent years. Although it is clear that dopamine (DA) agonists cannot completely rep lace levodopa therapy, they can be beneficial early in the course of P D by reducing the accumulation of DA which undergoes auto-oxidation an d generates cytotoxic free radicals. In the present study we demonstra te that pergolide, a widely used DA agonist, has free radical scavengi ng and antioxidant activities. Using a direct detection system for nit ric oxide radical (NO .) by electron spin resonance (ESR) spectrometry in an in vitro . NO-generating system, we examined the quenching effe cts of pergolide on the amount of NO . generated. Pergolide dose-depen dently scavenged NO .. In the competition assay, the IC50 value for pe rgolide was estimated to be about 30 mu M. Pergolide also dose-depende ntly attenuated the hydroxyl radical(OH) signal in an in vitro FeSO4-H 2O2 ESR system with an approximate IC50 value of 300 mu M. Furthermore , this agent significantly inhibited phospholipid peroxidation of rat brain homogenates in in vitro experiments and after repeated administr ation (0.5 mg/kg/24 h, i.p. for 7 days). Our findings suggest a neurop rotective role for pergolide on dopaminergic neurons due to its free r adical scavenging and antioxidant properties. (C) 1998 Elsevier Scienc e B.V.