Schapira A H, Obeso J A, Olanow C W
University Department of Clinical Neurosciences, Royal Free and University College Medical School, and Institute of Neurology, University College London, UK.
Neurology. 2000;55(11 Suppl 4):S65-8; discussion S69-71.
Catechol-O-methyl transferase (COMT) inhibitors block the peripheral metabolism of levodopa, increase its plasma half-life, and enhance its brain availability. Two COMT inhibitors, tolcapone and entacapone, have recently been made available as adjunctive agents to levodopa. In PD patients with motor fluctuations, they have been shown to increase "on" time and reduce "off" time. In patients with more advanced disease, they provide similar benefits, but patients tend to experience less overall benefit and a greater likelihood of developing dopaminergic adverse events. Accordingly, closer monitoring is required. In stable patients who have not yet developed motor complications, there are preliminary data suggesting that they experience improvements in motor function and in activities of daily living. Finally, there are theoretical reasons to consider administering a COMT inhibitor to patients from the onset of levodopa therapy in order to reduce the likelihood that motor complications will develop. COMT inhibitors are easy to administer, do not require titration, and are generally well tolerated particularly in patients with relatively mild disease. Adverse events are primarily dopaminergic and can usually be controlled by levodopa dose adjustments. COMT inhibitors have thus proven to be a useful addition to the therapeutic armamentarium of PD.
儿茶酚-O-甲基转移酶（COMT）抑制剂可阻断左旋多巴的外周代谢，延长其血浆半衰期，并提高其在脑内的可用性。两种COMT抑制剂，托卡朋和恩他卡朋，最近已作为左旋多巴的辅助药物上市。在有运动波动的帕金森病患者中，它们已被证明可增加“开”期时间并减少“关”期时间。在病情更严重的患者中，它们也有类似的益处，但患者总体获益往往较少，且发生多巴胺能不良事件的可能性更大。因此，需要更密切的监测。在尚未出现运动并发症的病情稳定的患者中，有初步数据表明他们的运动功能和日常生活活动有所改善。最后，从理论上讲，有理由在左旋多巴治疗开始时就考虑给患者使用COMT抑制剂，以降低发生运动并发症的可能性。COMT抑制剂易于给药，无需滴定，并且通常耐受性良好，尤其是在病情相对较轻的患者中。不良事件主要是多巴胺能的，通常可通过调整左旋多巴剂量来控制。因此，COMT抑制剂已被证明是帕金森病治疗药物中的一种有用补充。
