EFFECTS OF DOPAMINE-DERIVED ISOQUINOLINES ON HYDROXYL RADICAL FORMATION BY DOPAMINE AUTOXIDATION

The generation of hydroxyl radicals by dopamine and various dopamine-d erived isoquinolines, already detected or potentially present in human s, was studied in vitro upon incubation in phosphate buffer in the pre sence of salicylic acid and Fe++. The formation of hydroxyl radicals w as assessed by measuring the amount of 2,3- and 2,5-dihydroxybenzoic a cids formed in 20 min. The production of hydroxyl radicals by 6,7-dihy droxyisoquinolines was similar to that of dopamine, whereas 7-methoxy derivatives [(R)- and (S) salsoline] and two 6,7-dihydroxyisoquinolini um ions (1,2-DiMeDHIQ(+), 2-MeDHIQ(+)) generated significantly fewer h ydroxyl radicals. When dopamine (2.5 mu M) was co-incubated with vario us concentrations of(R)- and (S)salsolinol, (R)- and (S)tetrahydropapa veroline, N-methyl(S)salsolinol, or 1,2-dimethyl-6,7-dihydroxyisoquino linium ion, a decreased formation of hydroxyl radicals was observed as compared with that caused by dopamine alone, or with that expected if an additive effect of both radical promoters occurs. The possible inv olvement of endogenous isoquinolines in the pathogenesis of Parkinson' s disease is discussed in the light of these results.