Fariello Ruggero G
BioNeuroFar s.a.s, V. Della Vittoria 22 21016, Luino, Italy.
Neurotherapeutics. 2007 Jan;4(1):110-6. doi: 10.1016/j.nurt.2006.11.011.
Safinamide (SAF) ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino)propanamide) was initially synthetized by Farmitalia Carlo Erba (Italy). Following initial anticonvulsant screening, safinamide was selected for its potency, broad spectrum of action, and good safety margin. Pharmacodynamic properties probably relevant to its antiepileptic activity are use- and frequency-dependent block of voltage sensitive Na+ channels, block of Ca++ channels, and glutamate release inhibition. Possibly contributing mechanism are also selective and reversible monoamide oxidase B inhibition and dopamine and noradrenaline uptake inhibition. The high selectivity for the sigma-1 receptor site does not entail psychotomimetic or behavioral changes. In several experimental in vitro and in vivo conditions, SAF exerts neurorescuing and neuroprotectant effects. Safinamide is water soluble and suitable for 1 times a day oral administration in humans. In a pilot phase II study in 38 refractory epilepsy patients affected by multiple types of seizures, 41% of subjects obtained > or =50% seizure reduction during a 12-week escalating dose up to 300 mg 1 times day compared with perspective baseline. Safinamide is being developed in phase III for treatment of Parkinson's disease, whereas the development in epilepsy relates to the industrial strategy of the company.
沙芬酰胺（SAF）（(S)-(+)-2-(4-(3-氟苄氧基)苄基氨基)丙酰胺）最初由意大利法玛西亚卡罗埃巴公司合成。在最初的抗惊厥筛选后，沙芬酰胺因其效力、广泛的作用谱和良好的安全范围而被选中。与其抗癫痫活性可能相关的药效学特性包括对电压敏感钠通道的使用和频率依赖性阻滞、钙通道阻滞以及谷氨酸释放抑制。可能的作用机制还包括选择性和可逆性单胺氧化酶B抑制以及多巴胺和去甲肾上腺素摄取抑制。对σ-1受体位点的高选择性不会导致拟精神病或行为改变。在多种体外和体内实验条件下，SAF发挥神经挽救和神经保护作用。沙芬酰胺可溶于水，适合人类每日一次口服给药。在一项针对38名受多种类型癫痫发作影响的难治性癫痫患者的II期试点研究中，与预期基线相比，41%的受试者在为期12周、剂量递增至每日一次300毫克的过程中癫痫发作减少≥50%。沙芬酰胺正在进行III期开发用于治疗帕金森病，而其在癫痫方面的开发与该公司的产业战略有关。
