3-O-methyldopa blocks dopa metabolism in rat corpus striatum

3-O-Methyldopa (OMD) given to rats inhibits striatal uptake and utilization of L-dopa. Thus, the accumulation of L-dopa, dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in OMD-pretreated rats after L-dopa injection is significantly lower compared with control rats. This effect of OMD is dose-dependent. OMD inhibits L-dopa accumulation in the striatum after inhibition of aromatic amino acid decarboxylase activity with 3-hydroxybenzylhydrazine-HCL. This effect is not mediated through inhibition of firing in dopaminergic neurons, since the accumulation of dopamine in the striatum after gamma-butyrolactone injection was also significantly reduced by OMD. It is suggested that OMD competes with L-dopa and tyrosine uptake into the brain. These findings are in line with clinical observations which indicate that high plasma levels of OMD in parkinsonian patients are associated with poor response to L-dopa. The data presented here indicate that use of catechol-O-methyltransferase inhibitors with L-dopa may be of value in the treatment of parkinsonian patients.