SCAVENGING EFFECTS OF DOPAMINE AGONISTS ON NITRIC-OXIDE RADICALS

It has recently been considered that free radicals are closely involve d in the pathogenesis of Parkinson's disease (PD), and the level of ni tric oxide radical (. NO), one of the free radicals, is reported to in crease in PD brain. In the present study, we established a direct dete ction system for . NO in an in vitro . NO-generating system using drox y-1-methylethyl-2-nitrosohydrazino)-N-methyl-1 -propanamine as an . NO donor and rboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO) by electron spin resonance (ESR) spectrometry acid exam ined the quenching effects of the dopamine agonists pergolide and brom ocriptine on the amount of . NO generated. . NO appeared to be scaveng ed by pergolide and, to a lesser extent, by bromocriptine. In the comp etition assay, the 50% inhibitory concentration values for pergolide a cid bromocriptine were estimated to be similar to 23 and 200 mu M resp ectively. It was previously reported that in vivo treatment of pergoli de and bromocriptine completely protected against the decrease in leve ls of striatal dopamine and its metabolites in the B-hydroxydopamine-i njected mouse. Considering these findings, pergolide and probably brom ocriptine may also protect against dysfunction of dopaminergic neurons because of its multiple effects; not only does it stimulate the presy naptic autoreceptors, but it also directly scavenges . NO radicals and hence protects against . NO-related cytotoxicity. This ESR spectromet ry method using carboxy-PnO may be useful for screening other drugs th at can quench . NO.