メシル酸ラサジリン 化學(xué)特性,用途語(yǔ),生産方法
外観
白色～ほとんど白色粉末～結(jié)晶
効能
パーキンソン病治療薬, モノアミン酸化酵素B(MAO-B)阻害薬
商品名
アジレクト (武田薬品工業(yè))
説明
Rasagiline mesylate is a potent and selective irreversible
monoamine oxidase B (MAO-B) inhibitor launched in 2005
in Israel by Teva as monotherapy in patients with early Parkinson's
disease and as adjuvant treatment in moderate-toadvanced
disease. Lundbeck will market the drug
throughout Europe. Rasagiline is in phase II clinical trials at
Teva and Eisai for the treatment of Alzheimer's type dementia.
化學(xué)的特性
White to Off-White Crystalline Solid
使用
Rasagiline Mesylate is a new MAO-B inhibitor for the treatment of idiopathic Parkinson's disease.
適応癥
Rasagiline mesylate is a novel, potent, second-generation, selective, irreversible MAO-B inhibitor that blocks the breakdown of dopamine. It is approved for the treatment of PD. Indications for use of once-daily rasagiline are as a monotherapy in early PD and as an adjunct to levodopa in moderate to advanced disease. Rasagiline significantly improves symptoms during initial monotherapy in patients with early PD and as an adjunct treatment to levodopa in moderate-to-advanced patients. Rasagiline is well tolerated up to doses as high as 20 mg/day. Evidence for neuroprotective effect of rasagiline is as follows (Jain 2010c):
Structure activity studies have shown that the neuroprotective activity is associated with the propargyl moiety of rasagiline, which protects mitochondrial viability.
Experimental evidence supports rasagiline's neuroprotective efficacy, showing that neuronal survival is related to the anti-apoptotic properties of its propargyl moiety.
Aminoindan metabolite of rasagiline has been shown to have neuroprotective properties (Bar-Am et al. 2010).
一般的な説明
Rasagiline mesylate, (R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine methanesulfonate(Azilect), belongs to the propargylamine family and is a whiteto off-white powder, soluble in water or ethanol, slightly solublein isopropanol. Rasagiline is rapidly absorbed. Plasmaprotein binding for rasagiline ranges from 88% to 94%, withspecific binding to serum albumin being 61% to 63%. It undergoescomplete biotransformation before excretion, mainlyvia N-dealkylation and hydroxylation, to yield three majormetabolites: 1(R)-aminoindan, 3-hydroxy-N-propargyl-1-aminoindan, and 3-hydroxy-1-aminoindan. Both oxidativepathways are catalyzed by cytochrome P450 (CYP) enzymes,mainly the 1A2 isozyme. Rasagiline and its metabolites undergoglucuronide conjugation with subsequent urinary excretion.Inhibitors of the CYP1A2 may increase plasmaconcentrations of rasagiline up to twofold. Because rasagilineis a selective and irreversible inhibitor of MAO-B, itsduration of action is independent of the drug’s half-life and isinstead determined by the regeneration rate of MAO-B. Thischaracteristic is potentially beneficial in PD, where rasagiline’sprolonged effect may be able to limit the fluctuating responsesthat are characteristic of long-term drug treatmentwith levodopa.
作用機(jī)序
The specific mechanism of action of Rasagiline mesylate is unknown. One of these mechanisms is thought to be related to its MAO-B inhibitory activity, which leads to elevated extracellular dopamine levels in the striatum. It irreversibly blocks dopamine metabolism, thereby increasing dopamine levels, which can be beneficial for symptoms in Parkinson's disease patients.
メシル酸ラサジリン 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品