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Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease.
Mov Disord. 1997 Jul; 12(4):497-505.MD

Abstract

The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline 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, repeated 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 oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p < 0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest 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 confirm this finding.

Authors+Show Affiliations

Department of Neurology, University of Helsinki, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9251066

Citation

Lyytinen, J, et al. "Simultaneous MAO-B and COMT Inhibition in L-Dopa-treated Patients With Parkinson's Disease." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 12, no. 4, 1997, pp. 497-505.
Lyytinen J, Kaakkola S, Ahtila S, et al. Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease. Mov Disord. 1997;12(4):497-505.
Lyytinen, J., Kaakkola, S., Ahtila, S., Tuomainen, P., & Teräväinen, H. (1997). Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease. Movement Disorders : Official Journal of the Movement Disorder Society, 12(4), 497-505.
Lyytinen J, et al. Simultaneous MAO-B and COMT Inhibition in L-Dopa-treated Patients With Parkinson's Disease. Mov Disord. 1997;12(4):497-505. PubMed PMID: 9251066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous MAO-B and COMT inhibition in L-Dopa-treated patients with Parkinson's disease. AU - Lyytinen,J, AU - Kaakkola,S, AU - Ahtila,S, AU - Tuomainen,P, AU - Teräväinen,H, PY - 1997/7/1/pubmed PY - 1997/7/1/medline PY - 1997/7/1/entrez SP - 497 EP - 505 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 12 IS - 4 N2 - The effect of selegiline (L-deprenyl) on plasma catecholamines, clinical response, and drug tolerability was studied in 13 patients with Parkinson's disease (PD) treated with L-Dopa/benserazide and entacapone, a peripheral catechol-O-methyltransferase (COMT) inhibitor, in a placebo-controlled double-blind study. An L-Dopa test was performed on 3 study days. The first study day was with L-Dopa/benserazide only (control), the second after 14 days of treatment with 200 mg entacapone taken concomitantly with L-Dopa/benserazide in combination with either selegiline (10 mg daily) or placebo. After a 2-week washout period, selegiline 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, repeated 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 oxidase B (MAO-B) and COMT enzyme activities were measured from platelets and erythrocytes, respectively. Entacapone improved the clinical response to L-Dopa during both selegiline and placebo (p < 0.001) treatments. The improvement was more marked during combined selegiline and entacapone treatment than with entacapone alone (p < 0.01). Entacapone significantly increased plasma L-Dopa and DOPAC levels and decreased plasma 3-OMD and MHPG levels both with selegiline and placebo. Selegiline partially inhibited the entacapone-induced increase of plasma DOPAC. Plasma dopamine and noradrenaline levels did not change. Entacapone decreased erythrocyte COMT activity by > 35% (p < 0.001), and platelet MAO-B activity was almost completely inhibited by selegiline (p < 0.001). One patient withdrew because of diarrhea, dizziness, and loss of sleep when receiving selegiline treatment. Otherwise no differences in adverse events, mean daily blood pressures, or other safety parameters were observed between selegiline and placebo treatments. Our results suggest 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 confirm this finding. SN - 0885-3185 UR - https://www.unboundmedicine.com/medline/citation/9251066/Simultaneous_MAO_B_and_COMT_inhibition_in_L_Dopa_treated_patients_with_Parkinson's_disease_ L2 - https://doi.org/10.1002/mds.870120404 DB - PRIME DP - Unbound Medicine ER -