Catechol-O-methyltransferase inhibition increases striatal L-dopa and dopamine: An in vivo study in rats

Timothy Brannan, Julién Martínez-Tica, Melvin D. Yahr

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)683-685
Number of pages3
JournalNeurology
Volume42
Issue number3
DOIs
StatePublished - Mar 1992

ASJC Scopus subject areas

  • Clinical Neurology

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