3Omethyldopa

3-O-methyldopa, commonly abbreviated as 3-OMD, is a peripheral metabolite of the Parkinson’s disease drug levodopa (L-dopa). It is formed when the enzyme catechol-O-methyltransferase (COMT) adds a methyl group to the meta-hydroxyl of L-dopa, producing 3-O-methyldopa. This reaction occurs mainly in peripheral tissues such as the liver and gut, rather than in the brain.

In clinical and pharmacological contexts, 3-OMD is considered a major circulating product of L-dopa metabolism. Its formation competes with the central availability of L-dopa for conversion to dopamine, thereby potentially reducing the amount of L-dopa that reaches the brain and contributing to variability in motor response. The level of 3-OMD in plasma or urine can reflect the extent of peripheral L-dopa metabolism and overall COMT activity in an individual.

Management and therapeutic implications: COMT inhibitors, such as entacapone or tolcapone, reduce the peripheral methylation of L-dopa, thereby lowering 3-OMD formation. This can increase the bioavailability of L-dopa to the brain and help smoothen motor fluctuations in some patients undergoing L-dopa therapy. Measurement of 3-OMD levels may be used in research or clinical settings to assess COMT activity or L-dopa metabolism, but it is not used as a standalone diagnostic marker.

See also: Levodopa, catechol-O-methyltransferase inhibitors, Parkinson’s disease, dopaminergic therapy.