Which COMT inhibitor is often used with levodopa in advanced Parkinson's Disease and may cause liver damage?

Tolcapone is the COMT inhibitor commonly used in conjunction with levodopa for patients with advanced Parkinson's disease. It functions by inhibiting catechol-O-methyltransferase (COMT), an enzyme that metabolizes levodopa in the periphery, thereby increasing the availability of levodopa for conversion to dopamine in the brain. This is particularly useful in addressing the fluctuations in motor control experienced by patients in later stages of Parkinson's.

One significant concern with tolcapone is its potential for hepatotoxicity; it has been associated with elevated liver enzymes and liver damage in some patients. Because of this risk, patients receiving tolcapone require regular monitoring of liver function tests to catch any signs of liver injury early. This risk distinguishes tolcapone from other COMT inhibitors like entacapone, which is also used with levodopa but has a much lower risk of liver-related side effects. Other options, such as selegiline and amantadine, work through different mechanisms and do not primarily inhibit COMT, which further solidifies the specific role of tolcapone in the treatment of advanced Parkinson’s disease.