Tolcapone increases plasma catecholamine levels in patients with Parkinson's disease

Tolcapone is a catechol-ortho-methyl-tranferase (COMT) inhibitor that incre ases the L-DOPA half-life and the duration of effect in Parkinson's disease . We investigated the effect of tolcapone on the plasma catecholamine level s. We measured plasma catecholamines 2 h after the first daily dose of L-DO PA or L-DOPA + tolcapone while resting and 2 and 10 min after standing. We also measured the pharmacokinetics of L-DOPA and 3-OM-DOPA and the clinical response to the medication for 6 h after the early morning dose. The level s of dopamine, norepinephrine, adrenaline and total catecholamines signific antly increased and 3-OM-DOPA decreased with tolcapone. We did not observe significant changes in the plasma L-DOPA levels at the doses of tolcapone u sed in this study. Tolcapone side effects included worsening of dyskinesia and psychosis, diarrhea and elevation of liver enzymes. Twenty-four-hour am bulatory recording of arterial blood pressure and heart rate did not reveal cardiovascular side effects in patients treated with tolcapone for less th an I year. Since adrenergic stimulation may increase the hepatotoxic potent ial of commonly used drugs, usually thought of as safe for the liver, we po stulate that some of the already reported life threatening complications of tolcapone could be related to excessive adrenergic stimulation by high cat echolamine levels caused by inhibition of COMT activity. (C) 2001 Elsevier Science Ltd. All rights reserved.