SIMULTANEOUS MAO-B AND COMT INHIBITION IN L-DOPA-TREATED PATIENTS WITH PARKINSONS-DISEASE

The effect of selegiline (L-deprenyl) on plasma catecholamines, clinic al response, and drug tolerability was studied in 13 patients with Par kinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a place bo-controlled double-blind study. An L-Dopa test was performed on 3 st udy days. The first study day was with L-Dopa/benserazide only (contro l), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either sele giline (10 mg daily) or placebo. After a 2-week washout period, selegi line and placebo treatments were switched, and the third study day was after 14 days of treatment. During the study days, clinical response was evaluated at 30-min intervals for 6 h, by using the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, re peated blood pressure measurements were made, and plasma samples were taken for analysis of L-Dopa, 3-O-methyldopa (3-OMD), dihydroxyphenyl acetic acid (DOPAC), homovanillic acid (HVA), dopamine, noradrenaline, and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG). Monoamine oxidas e B (MAO-B) and COMT enzyme activities were measured from platelets an d erythrocytes, respectively. Entacapone improved the clinical respons e to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entaca pone treatment than with entacapone alone (p < 0.01). Entacapone signi ficantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline pa rtially inhibited the entacapone-induced increase of plasma DOPAC. Pla sma dopamine and noradrenaline levels did not change. Entacapone decre ased erythrocyte COMT activity by >35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). O ne patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adver se events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results sugge st that entacapone can be safely administered together with L-Dopa and selegiline in patients with PD, although further studies with larger number of patients and longer treatment periods are necessary to confi rm this finding.