Stocchi F, Vacca L, Grassini P, De Pandis M F, Battaglia G, Cattaneo C, Fariello R G
IRCCS San Raffaele Pisana, Rome, Italy.
Neurology. 2006 Oct 10;67(7 Suppl 2):S24-9. doi: 10.1212/wnl.67.7_suppl_2.s24.
In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.
在一项开放性试点研究中，给13名帕金森病患者服用了沙芬酰胺剂量（每天一次100、150和200毫克，高于先前测试剂量），同时给予稳定剂量的多巴胺（DA）激动剂，在8周期间，统一帕金森病评定量表（UPDRS）第三部分评估显示运动性能有显著的逐步改善（4.2分；P<0.001）。在另一组患者（N = 11）中，与左旋多巴联合使用相同剂量的沙芬酰胺可显著减少运动波动（UPDRS第四部分，2.1分；P<0.001），同时左旋多巴曲线下面积呈剂量比例增加，最高可达基线的77%。由于在所有测试剂量下MAO - B均被完全抑制（95%），我们认为这些生化和症状性剂量依赖性效应必定与其他作用机制有关，如抑制谷氨酸释放、增加多巴胺释放或抑制多巴胺再摄取。这些假设正在研究中，并将在对照临床试验中寻求证实。
