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Catechol-O-methyltransferase inhibition increases striatal L-dopa and dopamine

An in vivo study in rats

Department of Neurology, Mount Sinai School of Medicine, New York, NY.

We administered Ro 40–7592, an inhibitor of the enzyme catechol-O-methyltransferase (COMT) that crosses the blood-brain barrier, to rats and monitored extracellular catecholamine levels in the corpus striatum before and after the intraperitoneal administration of a bolus of 1-dopa. Acute administration of Ro 40–7592 increased basal levels of 1-dopa and dihydroxyphenylacetic acid (DOPAC) and decreased basal homovanillic acid (HVA) levels, but did not affect basal dopamine levels. In rats treated with Ro 40–7592, 1-dopa administration produced a greater increase in striatal levels of 1-dopa, dopamine, and DOPAC than it did in controls, while HVA formation was attenuated. We conclude that inhibition of COMT activity promotes central dopamine synthesis and release following administration of pharmacologic doses of 1-dopa.

Address correspondence and reprint requests to Dr. Timothy Brannan, Department of Neurology, Mount Sinai School of Medicine, Box 1137, New York, NY 10029.

Dr. Martínez-Tica is a recipient of a research fellowship award from the Int. Fed. of Park. Soc. NY, NY.

Received July 18, 1991. Accepted for publication in final form August 22, 1991.

This article has been cited by other articles:

				P. T. Mannisto and S. Kaakkola Catechol-O-methyltransferase (COMT): Biochemistry, Molecular Biology, Pharmacology, and Clinical Efficacy of the New Selective COMT Inhibitors Pharmacol. Rev., December 1, 1999; 51(4): 593 - 628. [Abstract] [Full Text] [PDF]