Lyytinen J, Kaakkola S, Ahtila S, Tuomainen P, Teräväinen H
Department of Neurology, University of Helsinki, Finland.
Mov Disord. 1997 Jul;12(4):497-505. doi: 10.1002/mds.870120404.
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.
在一项安慰剂对照双盲研究中，对13例接受左旋多巴/苄丝肼和外周儿茶酚-O-甲基转移酶（COMT）抑制剂恩他卡朋治疗的帕金森病（PD）患者，研究了司来吉兰（L-司立吉林）对血浆儿茶酚胺、临床反应及药物耐受性的影响。在3个研究日进行了左旋多巴试验。第一个研究日仅给予左旋多巴/苄丝肼（对照），第二个研究日是在14天的治疗后，同时服用200 mg恩他卡朋与左旋多巴/苄丝肼，并联合司来吉兰（每日10 mg）或安慰剂。经过2周的洗脱期后，司来吉兰和安慰剂治疗进行了切换，第三个研究日是在14天治疗后。在研究日期间，每隔30分钟评估6小时的临床反应，采用统一帕金森病评定量表（UPDRS）的运动评分。此外，进行了多次血压测量，并采集血浆样本分析左旋多巴、3-O-甲基多巴（3-OMD）、二羟基苯乙酸（DOPAC）、高香草酸（HVA）、多巴胺、去甲肾上腺素和3-甲氧基-4-羟基苯乙二醇（MHPG）。分别从血小板和红细胞中测量单胺氧化酶B（MAO-B）和COMT酶活性。在司来吉兰和安慰剂治疗期间，恩他卡朋均改善了对左旋多巴的临床反应（p<0.001）。联合司来吉兰和恩他卡朋治疗期间的改善比单独使用恩他卡朋更明显（p<0.01）。恩他卡朋在与司来吉兰和安慰剂联合使用时，均显著提高了血浆左旋多巴和DOPAC水平，并降低了血浆3-OMD和MHPG水平。司来吉兰部分抑制了恩他卡朋诱导的血浆DOPAC升高。血浆多巴胺和去甲肾上腺素水平未发生变化。恩他卡朋使红细胞COMT活性降低>35%（p<0.001），司来吉兰几乎完全抑制了血小板MAO-B活性（p<0.001）。1例患者在接受司来吉兰治疗时因腹泻、头晕和失眠而退出。否则，在司来吉兰和安慰剂治疗之间，未观察到不良事件、平均每日血压或其他安全参数的差异。我们的结果表明PD患者中恩他卡朋可与左旋多巴和司来吉兰安全联用，尽管需要更多患者和更长治疗期的进一步研究来证实这一发现。
