ANTIPARKINSONIAN THERAPIES AND BRAIN MITOCHONDRIAL COMPLEX-I ACTIVITY

Alterations in complex I activity, one of the enzymatic units of the m itochondrial respiratory chain, have been demonstrated in different ti ssues from patients with Parkinson's disease (PD). Subsequently, we sh owed that the chronic administration of levodopa can cause alterations in mitochondrial respiratory chain activity in rats, which suggests t hat the observed deficit in complex I activity in PD might be, at leas t in part, related to chronic levodopa therapy. Our study assessed the in vitro effects of different antiparkinsonian agents on complex I ac tivity in rat brain. As previously reported, both levodopa and dopamin e inhibit complex I activity in a dose-dependent manner. In contrast, the two major metabolites of dopamine, homovanillic acid and 3,4-dihyd roxyphenylacetic acid as well as 3-O-methyl-dopa, had little or no eff ect on complex I activities. Bromocriptine, pergolide, trihexyphenidyl , molindone, and clozapine were all without significant inhibitory eff ects on mitochondrial function. Although vitamin C and deprenyl did no t alter complex I activity, they did prevent the inhibitory effect of both levodopa and dopamine on complex I activity. This work indicates that among the different and usual antiparkinsonian agents, only levod opa and dopamine induced reductions in complex I activity. It also ind icates that vitamin C and deprenyl are both effective in preventing th e levodopa-induced complex I inhibition. This latter finding provides further support to the use of antioxidants and monoamine oxidase inhib itors as therapeutic strategies in attempts to slow the progression of PD.