COMT inhibitors in Parkinson's disease

The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson 's medications. By inhibiting the enzyme catechol-o-methyl-transferase (COM T), they prevent peripheral degradation of levodopa, allowing a higher conc entration to cross the blood-brain barrier. Pharmacokinetic studies have sh own that both tolcapone and entacapone significantly prolong the eliminatio n half life, and increase the area under the curve of levodopa without incr easing C max. Clinical studies with COMT inhibitors have shown benefit in b oth stable and fluctuating PD patients with improvement in motor function w ith lower levodopa doses. fluctuating patients also had increased "on" time and reduced "wearing off". Side effects were most commonly related to incr eased dopaminergic stimulation. Specific side effects included diarrhea and elevated liver enzymes. The recent reports of three cases of fulminant hep atitis with the use of tolcapone has led many countries to remove this comp ound from their market. Concerns about a possible class effect should impos e close monitoring of liver function tests with the use of any of the nitro catechols.