雷沙吉兰Rasagiline-改善帕金森氏病各阶段运动症状
随着老龄人口的增多,帕金森氏病发病率上升,患病总人口增加；根据广州的统计,有6成多的帕金森氏病患者没有接受药物治疗,这表明有很大比例的帕金森氏病患者未就医,或未接受治疗。左旋多巴依然是目前临床最为有效的帕金森氏病治疗药物,为帕金森氏病药物治疗的“金标准”。

2005年6月27日泰瓦公司和Lundbeck公司宣布,治疗帕金森氏症的雷沙吉兰(Rasagiline,Azilect)已获准在英国上市,2007年07月12日医学空间(MEDcyber.com)7月12日消息--纽约的研究人员近期在美国神经病协会的第131届年会上指出,已接受左旋多巴治疗的帕金森氏病可从添加雷沙吉兰Rasagiline(第二代单胺氧化酶B型抑制剂)治疗中获益。雷沙吉兰被EMEA批准单独或与L-DOPA联合使用治疗处于剂末波动(end-of-dosefluctuations)状态的原发性帕金森氏病患者。雷沙吉兰是强活性的、选择性的、不可逆MAO-B抑制剂,雷沙吉兰不会产生amphetamine类代谢物。事实上,其主要代谢产物1(R)-aminoindan还具有保护作用。动物模型上显示出良好的抗帕金森氏病和运动功能修复活性外,雷沙吉兰还具有神经保护特性。因此雷沙吉兰被认为在治疗PD方面比selegiline更有优势。

共有253名单用左旋多巴治疗的帕金森氏病患者入组该项研究,其中133人添加了雷沙吉兰治疗,120人继续单用左旋多巴治疗。结果发现,联合治疗组患者的“关”时间平均减少了1.44小时；单药治疗组则平均减少了0.66个小时,两者差别达到了显著的统计学意义。在对217名症状轻度波动的患者进行进一步分层分析后发现,接受联合治疗的患者的“关”时间平均减少了0.76个小时；单药治疗的患者则平均增加了0.22个小时,两者的差异有显著的统计学意义。研究人员指出,雷沙吉兰作为左旋多巴的辅助治疗能有效改善帕金森氏病患者的临床症状,且安全性良好。

早期帕金森氏病患者随机接受雷沙吉兰(1或2mg)或安慰剂治疗。6个月后,安慰剂转换为雷沙吉兰(2mg)。所有病人都完成12个月的随访期。所有给予rasagilne的病人以UPDRS评价都有症状改善,但一开始就接受雷沙吉兰治疗的患者其效果持续12个月。
,雷沙吉兰每日服用一次,雷沙吉兰可作为早期帕金森氏症患者的单一治疗,也可作为中晚期帕金森氏症患者的辅助治疗,雷沙吉兰的优势是每日只需口服一次,剂量不需要滴定,以及很好的耐受性。中到重度病人接受L-DOBA治疗的基础上加用雷沙吉兰可改善症状以及运动波动(motorfluctuations)。雷沙吉兰的最重要的优势是可以在早期阶段限制神经变性。为期一年的由早期帕金森氏病人参加的临床试验显示雷沙吉兰可能具有神经保护效果,有可能可改善帕金森氏病的进程。

3项有1000名患者参加的临床试验考察了雷沙吉兰单独或作为L-DOPA的辅助治疗对PD的疗效。第一项试验持续26周,参加者是新诊断的,尚未经过药物治疗的PD患者。患者随机接受安慰剂(138人)或雷沙吉兰(1mg/day,134人)或雷沙吉兰(2mg/day,132人)。雷沙吉兰两个剂量组在首要有效性终点方面都显著优于安慰剂组。雷沙吉兰1mg组患者统一帕金森氏病登记量表(UPDRS,partsI–III)总分较基线值的改变值平均为-4.2(和安慰剂相比),雷沙吉兰2mg组为-3.6。由帕金森氏病生活质量量表(PD-QUALIF)所评价的生活质量,雷沙吉兰也要显著优于安慰剂。第二项试验持续18周,患者随机接受安慰剂(229人)、雷沙吉兰(1mg/day,231人)或entacapone200mg++L-DOPA/脱羧酶抑制剂(227人)的治疗。第三项试验持续26周,病人随机接受安慰剂(159人)、雷沙吉兰(0.5mg/day或1mg/day；164人和149人)的治疗。两个试验的首要有效性终点都是一天内,处于“off”状态的平均小时数较基线值的改变。第二项试验中,和安慰剂相比,雷沙吉兰组的差异值为-0.78小时；第三项试验的差异值为-0.94小时。

雷沙吉兰(Rasagiline)在对Aβ25-35诱导PC12细胞凋亡的防护作用的研究中,目的探讨雷沙吉兰(Rasagiline)对β-淀粉样蛋白(Aβ)诱导PC12细胞损伤阿尔茨海默病(AD)模型的保护作用及其机制.方法不同浓度的Aβ25-35(1μmol/L,10μmo1/L,20μmol/L)作用于PC12细胞48h,MTT法检测细胞存活率,选用使细胞存活率降低到64％的Aβ浓度20μmol/L.用不同浓度的雷沙吉兰(0.1μmo1/L,1μmol/L,10μmol/L)预孵育PC12细胞1h,再加入20μmol/L的Aβ共孵育48h,再测MTT活性,并用荧光染料丫啶橙和溴化乙啶染色,在荧光显微镜下计数凋亡细胞检测凋亡细胞百分率.结果Aβ在20μmol/L时使PC12细胞存活率降低至64％,与对照组差异显著,1μmol/L的雷沙吉兰可显著提高细胞存活率至85％.对照组细胞凋亡率为2％,20μmol/LAβ作用48h后,PC12细胞凋亡率达13％,1μmol/L的雷沙吉兰使20μmol/LAβ诱导的PC12细胞凋亡率下降到5％.结论雷沙吉兰对Aβ引起的PC12细胞损伤具有明显的保护作用,其机制可能与抑制Aβ诱导的凋亡有关.

雷沙吉兰对于帕金森氏病治疗是一个重要进展,它可以改善帕金森氏病各个阶段的运动方面症状,而且每日只需口服一次,耐受性也很好.

价格：30Tablet    Azilect  1mg 
价格：100Tablet  Azilect  1mg 

Azilect® Azilect® (rasagiline tablets) is Teva's second innovative drug, indicated for the treatment of Parkinson's disease, both as initial monotherapy in the early stage of the disease and as an adjunct to levodopa in moderate to advanced stages of the disease. Its development was based on original research performed in the Rappaport Research Institute, Technion, Haifa, Israel. Azilect® is a potent, second-generation, irreversible monoamine oxidase type B (MAO-B) inhibitor with neuroprotective activities demonstrated in various in vitro and in vivo studies. Its beneficial clinical effect, seen in the entire spectrum of the disease, combined with its once-daily dosing, lack of need for titration and high tolerability, allows Azilect® to address significant unmet needs in the treatment of Parkinson's disease. Azilect® Product Profile Azilect once daily is efficacious in the treatment of PD as monotherapy in early-disease, providing patients with dual benefit - both symptomatic effect, including motor symptoms, activities of daily living, and quality of life, as well as effect on slowing the clinical progression of the disease. Azilect® also has demonstrated efficacy as an adjunct therapy of PD: symptomatic control of PD and treatment of motor complications in moderate-to-advanced PD patients experiencing motor fluctuations. All effects were demonstrated on top of optimised anti-PD therapy. Azilect® has been proven to be safe and well tolerated in both monotherapy and adjunct therapy in PD patients of all ages, with low incidence of adverse events and low discontinuation rate. In contrast with most other treatments for PD, Azilect® has a simple dosing regimen of one tablet taken once daily at any time, with or without food, and it does not require titration. This combination of simple regimen and very good tolerability contributes to patients' compliance with treatment, and therefore to the success of treatment. Clinical Development of Azilect® Azilect® has demonstrated efficacy and safety in three pivotal studies that included over 1,500 patients with Parkinson´s disease at different stages of the disease. TEMPO - demonstrated the clinical efficacy of Azilect as monotherapy in early PD patients. Patients were also followed through an open-label long-term extension phase of over 6 years, confirming the safety and efficacy of early treatment with Azilect in the long term. LARGO - conducted in Europe, Israel and Argentina, and it's results showed high efficacy of Azilect as an adjunct therapy, given on top of other anti PD medications, with entacapone as an active comparator. PRESTO - performed in North America, results confirming the clinical efficacy of Azilect as adjunct therapy in moderate-to-advanced PD patients. Based on the results of these trials , Azilect was granted marketing approvals in the US, Canada, the EU , Israel, and some additional countries. Until recently, no treatment had ever been proven to slow the progression of Parkinson´s disease. The pharmacological strategy for the management of Parkinson´s disease has involved the use of drugs to reduce the motor symptoms of the disease and to otherwise bring symptomatic relief to patients. Based on the findings of the TEMPO and its open extension results, as well as the broad pre-clinical evidence for the neuroprotective effects of rasagiline, Teva initiated the ADAGIO (Attenuation of Disease progression with Azilect® Once-daily) study with AZILECT in November 2005. The ADAGIO study In June 2008, Teva announced the positive results of the ADAGIO study that was designed to explore the disease modifying effects of Azilect by slowing the rate of disease progression. ADAGIO is one of the largest ever trials in early PD patients. The study recruited 1176 very early PD patients in 14 countries in Europe, North America, Israel and Argentina. The trial used a novel delayed-start design with a 9 month, double-blind, placebo-controlled phase, and a second 9-month active treatment phase comparing the early-start cohort with the delayed-start cohort. AZILECT 1mg, the marketed dose worldwide, met all three endpoints of the primary analysis in a hierarchal manner, demonstrating that Azilect has a positive effect on slowing the clinical progression of PD. Slowing disease progression is currently one of the major unmet needs in PD, and Azilect is the first drug to show such an effect in a well designed prospective clinical study. Marketing and Distribution Azilect® was first launched in Israel, in March 2005, and shortly thereafter, in the first EU countries, the UK and Germany. In the USA, Azilect® was launched in July 2006. Presently, Azilect® is available in 32 countries. Teva has a long-term agreement for the joint development and marketing of Azilect in Europe and some additional markets with H. Lundbeck A/S. In North America, Azilect® is marketed by Teva's wholly-owned subsidiary Teva Neuroscience (www.tevaneuro.com). About Parkinson's Disease Parkinson's disease (PD) is a degenerative disorder of the central nervous system that impairs the sufferer's motor skills and speech. PD is both a chronic and progressive illness, which results in a marked decrease in the health-related quality of life of patients and their caregivers and places a tremendous economic burden on society. An estimated four million patients are affected by this chronic disease worldwide, which typically occurs at a late age, affecting approximately 1% of the population over the age of 65. 1 in 20 people diagnosed with PD is younger than 40 years. Selected Publications TEMPO: Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2002); 59(12):1937-1943 TEMPO delayed-start: Parkinson's Study Group (Siderowf A.): Arch. Neurolo. (2004); 61:561-566 LARGO: Rascol, O. et al.: Lancet (2005); 365:947-954 PRESTO: Parkinson's Study Group; Arch Neurol. (2005); 62:241-248. ADAGIO: Rationale, design, and baseline characteristics. Olanow CW et al: Mov Disord 2008; 23 (15): 2194 - 2201. For additional information about Azilect®, please see the product website: www.Azilect.com.