单胺氧化酶B抑制剂safinamide有望成为治疗帕金森病的特效药

默克雪兰诺公司（Merck Serono）和纽隆制药公司（Newron Pharmaceuticals）公布了对其合作开发的小分子单胺氧化酶B抑制剂safinamide进行的一项名为Study018的双盲、安慰剂对照的Ⅲ期临床研究结果。该实验为期18个月,尽管未完全达到研究的主要考察指标,但两家公司仍称该药有望成为治疗帕金森病的特效药。

Safinamide的首批Ⅲ期试验数据

Newron制药公司表示，其离子通道调节剂safinamide（Ⅰ）在改善帕金森病（PD）患者运动症状方面有统计学意义，对认知功能有积极作用，可在PD患者中用作多巴胺激动剂的辅助用药。

Safinamide受挫于帕金森病Ⅲ期研究

Newron制药／MerckSerono公司的离子通道调节剂safinamide（Ⅰ）在一项为期一年的用于帕金森病的Ⅲ期扩展试验中未达到主要终点。

Newron公司的Safinamide仍然是Merck Serono公司的“优先项目”

Newron制药公司的口服氨基酰胺衍生物safinamide（Ⅰ）仍然是MerckSerono公司的优先项目。

Type-B monoamine oxidase inhibitors in neurological diseases:clinical applications based on preclinical findings

Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.

具有开发潜力的抗帕金森病药

全球患帕金森病人数超过150万，开发具有较好疗效的药物成为市场迫切需要。以下为全球正在开发的并且具有潜力的抗帕金森病药。

国外制药企业新药研发动态

FDA批准Totect用于蒽环类抗生素外渗;Safinamide可改善早期帕金森病症状;宫颈癌疫苗cervarix获准在澳大利亚上市;欧洲批准第一个乳腺癌联合靶向治疗药Herceptin;Dkerb有望用于转移性乳腺癌一线治疗;

单胺氧化酶B抑制剂在治疗帕金森病中的研究

理想的帕金森病治疗药物应是既能缓解症状,又能减缓疾病的进展。Safinamide是一种新型单胺氧化酶B(MAO-B)抑制剂,目前正在用于抗痉挛、抗帕金森病和神经保护方面的研究。Safinamide具有独特的分子结构、多重作用机制和很高的治疗指数。它既能高效、选择性和可逆的抑制MAO-B的活性,又能阻断钠、钙通道和抑制谷氨酸的释放。Safinamide还具有极好的的生物利用度、线型动力学、较长的半衰期和良好的安全性及耐受性。本文对主要的MAO-B抑制剂作一介绍。