COMT inhibitors in Parkinson's disease

Abstract

The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson's medications. By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of levodopa, allowing a higher concentration to cross the blood-brain barrier. Pharmacokinetic studies have shown that both tolcapone and entacapone significantly prolong the elimination half life, and increase the area under the curve of levodopa without increasing C max. Clinical studies with COMT inhibitors have shown benefit in both stable and fluctuating PD patients with improvement in motor function with lower levodopa doses. Fluctuating patients also had increased "on" time and reduced "wearing off". Side effects were most commonly related to increased dopaminergic stimulation. Specific side effects included diarrhea and elevated liver enzymes. The recent reports of three cases of fulminant hepatitis with the use of tolcapone has led many countries to remove this compound from their market. Concerns about a possible class effect should impose close monitoring of liver function tests with the use of any of the nitrocatechols.