Catechol-O-methyltransferase and Parkinson's disease.

OMD inhibits L-DOPA utilization in rat corpus striatum. This effect is probably mediated through competition with L-DOPA for brain uptake mechanism. Such competition may explain the inhibition exerted by OMD on L-DOPA-induced rotation in rats with unilateral destruction of the nigrostriatal pathway. U-0521, a potent COMT inhibitor, was shown, after i.p. injection, to effectively block the accumulation of OMD in the plasma and to enhance L-DOPA metabolism in rat brain. This drug, however, was not active when given orally to rats and to a single patient with Parkinson's disease. It is suggested that the combined use of L-DOPA plus an orally active COMT inhibitor may be useful in future treatment of Parkinson's disease.