Olanow C Warren, Stocchi Fabrizio
Department of Neurology, Mount Sinai School of Medicine, New York, New York 10028, USA.
Neurology. 2004 Jan 13;62(1 Suppl 1):S72-81. doi: 10.1212/wnl.62.1_suppl_1.s72.
COMT inhibitors have historically been used as adjuncts to levodopa in fluctuating PD patients to increase "on" time and reduce "off" time. Evidence that motor complications are related to intermittent or pulsatile stimulation of striatal dopamine receptors has led to the use of long-acting dopaminergic therapies that provide more continuous dopaminergic stimulation (CDS). CDS-based therapies are associated with the prevention and reversal of levodopa-related motor complications in MPTP-lesioned primates and PD patients. However, levodopa remains the most effective and widely used anti-parkinsonian agent and is eventually required in all PD patients. The standard oral formulation of levodopa has a relatively short half-life and is associated with the development of motor complications when used as either initial or supplemental therapy. The CDS concept raises the possibility that administration of levodopa in combination with a COMT inhibitor to extend its half-life might reduce the risk of inducing motor complications. This article considers the possibility that combining levodopa with entacapone may prevent or reverse motor complications.
儿茶酚-O-甲基转移酶（COMT）抑制剂历来被用作左旋多巴的辅助药物，用于治疗症状波动的帕金森病（PD）患者，以增加“开”期时间并减少“关”期时间。有证据表明，运动并发症与纹状体多巴胺受体的间歇性或脉冲式刺激有关，这促使人们使用长效多巴胺能疗法，以提供更持续的多巴胺能刺激（CDS）。基于CDS的疗法与预防和逆转MPTP损伤的灵长类动物及PD患者中与左旋多巴相关的运动并发症有关。然而，左旋多巴仍然是最有效且应用最广泛的抗帕金森病药物，所有PD患者最终都需要使用它。左旋多巴的标准口服制剂半衰期相对较短，当用作初始治疗或补充治疗时，会引发运动并发症。CDS概念提出了一种可能性，即联合使用左旋多巴和COMT抑制剂来延长其半衰期，可能会降低引发运动并发症的风险。本文探讨了左旋多巴与恩他卡朋联合使用可能预防或逆转运动并发症的可能性。
