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CNS Pharmacology

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Question:

C. Catechol-O-methyltransferase inhibitors

Author: Suzuki



Answer:

Normally, the methylation of levodopa by catechol-O-methyltransferase (COMT) to 3-O-methyldopa is a minor pathway for levodopa metabolism. However, when peripheral dopamine decarboxylase activity is inhibited by carbidopa, a signifi cant concentration of 3-O-methyldopa is formed that competes with levodopa for active transport into the CNS. Inhibition of COMT by entacapone or tolcapone leads to decreased plasma concentrations of 3-O-methyldopa, increased central uptake of levodopa, and greater concentrations of brain dopamine. Both of these agents have been demonstrated to reduce the symptoms of “wearing-off ” phenomena seen in patients on levodopa–carbidopa.


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Suzuki
Suzuki