Stocchi Fabrizio, Torti Margherita
Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy.
Drug Des Devel Ther. 2016 Feb 5;10:609-18. doi: 10.2147/DDDT.S77749. eCollection 2016.
Safinamide (SAF) is a new drug developed for the treatment of Parkinson's disease (PD). It is a benzylamino derivative with multiple mechanisms of action and antiparkinsonian, anticonvulsant, and neuroprotective properties. SAF inhibits monoamine oxidase B and dopamine reuptake and glutamate release, blocks voltage-dependent sodium channels, and modulates calcium channels. Although the antiparkinsonian effect can be ascribed in part to the inhibition of the monoamine oxidase B, which is complete at 50 mg, the enhanced benefit seen at the 100 mg dose is probably due to nondopaminergic mechanisms. SAF will represent an important option for patients with both early and advanced PD. In early PD patients, the addition of SAF to dopamine agonists may be an effective treatment strategy to improve motor function, prolong the use of dopamine agonists, and/or delay the introduction of levodopa. In advanced parkinsonian patients, SAF has been demonstrated to significantly increase on time with no, or nontroublesome dyskinesias. All studies performed have demonstrated its efficacy in benefiting both short-term and long-term quality-of-life outcomes in both early and advanced PD patients. SAF has been investigated in long-term (24 months), double-blind, placebo-controlled studies, where it showed a very good safety profile. SAF has not been studied in de novo PD patients, and its potential positive effect on dyskinesia deserves further dedicated studies.
沙芬酰胺(SAF)是一种开发用于治疗帕金森病(PD)的新药。它是一种苄基氨基衍生物,具有多种作用机制以及抗帕金森、抗惊厥和神经保护特性。SAF抑制单胺氧化酶B、多巴胺再摄取和谷氨酸释放,阻断电压依赖性钠通道,并调节钙通道。虽然抗帕金森作用部分可归因于对单胺氧化酶B的抑制,该抑制在50毫克时达到完全抑制,但在100毫克剂量时观察到的增强益处可能归因于非多巴胺能机制。SAF将为早期和晚期PD患者提供一个重要选择。在早期PD患者中,将SAF添加到多巴胺激动剂中可能是一种有效的治疗策略,可改善运动功能、延长多巴胺激动剂的使用时间和/或延迟左旋多巴的引入。在晚期帕金森病患者中,已证明SAF可显著增加“开”期时间,且无或仅有轻微异动症。所有已进行的研究均表明其对早期和晚期PD患者的短期和长期生活质量结局均有有益作用。SAF已在长期(24个月)、双盲、安慰剂对照研究中进行了调查,结果显示其安全性良好。SAF尚未在初发PD患者中进行研究,其对异动症的潜在积极作用值得进一步专门研究。