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It has recently been considered that free radicals are closely involved in the pathogenesis of Parkinson's disease (PD), and the level of nitric oxide radical (N0), one of the free radicals, is reported to increase in PD brain. In the present study, we established a direct detection system for N0 in an in vitro •NO-generating system using 3-(2-hydroxy-1 -methylethyl-2-nitrosohydrazino)-N-methyl-1-propanamine as an N0 donor and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1 -oxyl 3oxide (carboxy-PTIO) by electron spin resonance (ESR) spectrometry and examined the quenching effects of the dopamine agonists pergolide and bromocriptine on the amount of N0 generated. N0 appeared to be scavenged by pergolide and, to a lesser extent, by bromocriptine. In the competition assay, the 50% inhibitory concentration values for pergolide and bromocriptine were estimated to be -23 and 200 j.tM, respectively. It was previously reported that in vivo treatment of pergolide and bromocriptine completely protected against the decrease in levels of striatal dopamine and its metabolites in the 6-hydroxydopamine-injected mouse. Considering these findings, pergolide and probably bromocriptine may also protect against dysfunction of dopaminergic neurons because of its multiple effects; not only does it stimulate the presynaptic autoreceptors, but it also directly scavenges N0 radicals and hence protects against N0related cytotoxicity. This ESR spectrometry method using carboxy-PTIO may be useful for screening other drugs that can quench N0. Key Words: Nitric oxide-Free radical-Pergolide-Dopamine agonist-Scavenging effect-2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide-Electron spin resonance.

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