Methionine Levodopa

Tolcapone and entacopone are reversible inhibitors of catechol-O-methyltransferase (COMT), which normally transfers a methyl group from the metabolic intermediate S-adenosyl-L-methionine to the 3-phenolic moiety of dopamine, resulting in inactivation of the neurotransmitter (Fig. 25.2). Therefore, because tolcapone and entacopone block the activity of COMT, they prolong the activity of dopamine. Because COMT also inactivates levodopa, COMT Inhibitors prolong the action of levodopa. (Fig. 25.2). 

The fluctuations in response to levodopa experienced by some patients may be due to the timing of meals and the type of diet, particularly the protein content, both of which can reduce the effects of levodopa. The effects of levodopa can be reduced by the amino acid methionine, and the blood levels of levodopa can be reduced by the amino acid tryptophan. 

The amino acid methionine is used therapeutically, and although information about its interaction with levodopa is very limited, it indicates that large doses of methionine should be avoided in patients being treated with levodopa. 

Pearce LA, Waterbury LD. L-methionine a possible levodopa antagonist. Neurology (1974) 24, 640-1. 

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