rMAO-B (IC50 = 4.43 nM); rMAO-A (IC50 = 412 nM)

用地塞米松 (10 µM) 处理后，SH-SY5Y 和 1242-MG 的增殖率经雷沙吉 (0.25 nM；96 小时) 显着增加[2]。

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1. 研究了罗沙吉兰[n -丙炔- 1r(+)-氨基吲哚胺]及其S(-)-对映体（TVP 1022）和外消旋化合物（AGN-1135）在大鼠体内的单胺氧化酶（MAO） A和B抑制剂活性，并与selegiline（1-去戊烯基）进行了比较。研究MAO抑制作用的组织为脑、肝和小肠。2. 虽然雷沙吉兰和AGN1135在体外和体内都是高效的选择性不可逆MAO抑制剂，但S（-）对映体在所检查的组织中相对不活跃。3. 雷沙吉兰对大鼠脑MAO活性的体外抑制IC（50）值分别为4.43+/-0.92 nM （B型）和412+/-123 nM （A型），单剂量雷沙吉兰对脑和肝脏MAO活性的体外抑制ED（50）值分别为0.1+/-0.01、0.042+/-0.0045 mg kg（-1）和6.48+/-0.81、2.38+/-0.35 mg kg（-1）。4. 在ED（50）值分别为0.014+/-0.002和0.013+/-0.001 mg kg（-1）的慢性（21天）口服剂量下，肝脏和大脑的选择性MAO-B抑制作用保持不变。5. 雷沙吉兰对MAO-B抑制的选择性程度与对MAO-A抑制的选择性程度相似。急性和慢性给药时，雷沙吉兰体内对大鼠脑和肝脏MAO-B的抑制效力是斯来吉兰的3 ~ 15倍，但在体外具有相似的效力。6. 这些数据加上选择性MAO-B抑制剂量的雷沙吉兰缺乏拟酪胺交感神经增强作用，表明这种抑制剂如斯来吉兰可能是治疗帕金森病的有效药物，无论是对症治疗还是左旋多巴辅助治疗，但缺乏安非他明样代谢物可能显示雷沙吉兰的治疗优势。[1]

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压力会影响大脑，导致抑郁；然而，分子发病机制尚不清楚。应激与应激引起的糖皮质激素分泌过高之间存在关联。据报道，地塞米松（一种合成糖皮质激素类固醇）可诱导细胞凋亡并增加单胺氧化酶（MAO）的活性（Youdim et al. 1989）。MAO是一种降解胺能神经递质的酶；多巴胺、去甲肾上腺素、血清素、膳食胺和MAO抑制剂是经典的抗抑郁药物。在这项研究中，我们用人神经母细胞瘤SH-SY5Y细胞和胶质母细胞瘤1242-MG细胞，比较了雷沙吉兰（Azilect）及其主要代谢物R-aminoindan与斯来吉兰（Deprenyl）预防地塞米松诱导的脑细胞死亡的能力。MTT试验显示，地塞米松降低了细胞活力，但雷沙吉兰、斯来吉兰和1- r -氨基肽可显著预防地塞米松诱导的脑细胞死亡。在三种药物中，雷沙吉兰的神经保护作用最高。此外，我们还观察了这些药物对MAO B催化活性和细胞凋亡DNA损伤的抑制作用（TUNEL染色）。雷沙吉兰对MAO - B酶活性的抑制作用和对DNA损伤的预防作用均优于selegiline和1- r -氨基酸。综上所述，雷沙吉兰较强的神经保护作用可能与其母体药物及其代谢物1- r -氨基氨基酸的联合作用有关。［2］

在多系统萎缩的转基因模型中，雷沙吉兰具有神经保护作用。根据运动行为测试，与 2.5 mg/kg 雷沙吉兰治疗相关的运动障碍有所改善[3]。

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本研究是利用本小组先前描述的转基因小鼠模型来测试雷沙吉兰作为多系统萎缩（MSA）疾病调节剂的潜力。（PLP） α -突触核蛋白转基因小鼠具有胶质细胞质包涵病理，通过3-硝基丙酸中毒来模拟成熟的msa样神经变性。使用两种剂量的雷沙吉兰（0.8和2.5 mg/kg），疗程为4周。通过评估运动行为和神经病理学，将雷沙吉兰治疗的动物与安慰剂盐治疗的小鼠进行比较。运动行为测试（包括极测试、步幅测试和一般运动评分评估）显示，2.5 mg/kg雷沙吉兰治疗可改善运动缺陷。免疫组织化学和组织学显示，注射2.5 mg/kg雷沙吉兰后，MSA小鼠纹状体、黑质致密部、小脑皮层、脑桥核和下橄榄中3- np诱导的神经元丢失明显减少。研究结果表明，雷沙吉兰在MSA转基因小鼠模型中具有神经保护作用，因此可能被认为是一种有希望的人类MSA疾病修饰候选药物。［3］

体外测定MAO抑制活性[1]
采用Tipton & Youdim（1983）的改进方法测定MAO-A和-B的活性。使用玻璃聚四氟乙烯电机驱动均质机（脑和肝脏）或Ultraturrax（肠道）将大鼠或人类大脑皮质组织在0.3 M蔗糖（1份组织至20份蔗糖）中均质。将待测抑制剂加入到0.05 M磷酸盐缓冲液（pH 7.4）中适当稀释的酶制剂中，与0.1 μM的selegiline（用于测定MAO-A）或0.1 μM的clorgyline（用于测定MAO-B）一起孵育。37℃孵育60 min后，分别加入标记底物（测定MAO-A的14c -5-羟色胺二硫酸肌酐100 μM，测定MAO-B的14c -苯乙胺10 μM），孵育30 min或20 min。然后加入柠檬酸（2 M）停止反应。将放射性代谢物提取到甲苯/乙酸乙酯（1:1 v v−1）中，加入2,5-二苯氧恶唑溶液，终浓度为0.4% (w v−1)，通过液体闪烁计数估算代谢物含量。药物存在时的活性表示为对照样品中活性的百分比。[1]
由于苯乙胺也能被MAO-A有效代谢（O’carroll et al., 1983），因此预孵育是在克罗吉兰或斯来吉兰存在的情况下进行的，这导致了MAO-B的抑制曲线，如果MAO-A未失活，斯来吉兰或Rasagiline/雷沙吉兰对MAO-B的抑制在80%左右时达到平台期 。因此，为了比较对MAO-A和MAO-B具有潜在不同抑制作用的两种抑制剂，认为有必要在测定前采用相反酶形式灭活的系统。

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催化活性测定[1]
SH-SY5Y和1242-MG细胞培养融合，收获，用磷酸盐缓冲盐水洗涤。100微克总蛋白与10µM 14c标记的苯乙胺在37℃的实验缓冲液（50 mM磷酸钠缓冲液，pH 7.4）中孵育20分钟，加入100µl 6n HCl终止。然后用乙酸乙酯/甲苯（1:1）萃取反应产物，4℃离心10 min，提取含有反应产物的有机相，用液体闪烁光谱法测定其放射性。

细胞活力测定[2]
细胞类型：神经母细胞瘤 SH-SY5Y 和胶质母细胞瘤 1242- MG
测试浓度： 0.25 nM
孵育持续时间： 96 小时
实验结果： 使用地塞米松处理的 SH-SY5Y 细胞的细胞增殖率增加约 60%。用地塞米松处理的 1242-MG 细胞的细胞增殖率增加约 35%。

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细胞培养与处理[2]
将SH-SY5Y和1242-MG细胞接种于6孔板中，在培养基中培养过夜。将细胞添加无类固醇的炭剥离胎牛血清约6小时，然后在炭剥离胎牛血清存在的情况下，将培养基替换为含有10µM地塞米松、0.25 nM 罗沙吉兰、0.25 nM selegiline或1µM 1- r -氨基酸的培养基。每隔一天治疗一次，连续4天。

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TUNEL试验[2]
采用末端脱氧核苷酸转移酶（TdT）介导的dUTP Nick End Labeling (TUNEL) assay来评估处理细胞的凋亡程度。简单地说，在实验前一天将细胞镀在四孔室载玻片上，分别用或不加10µM地塞米松、0.25 nM的 雷沙吉兰、0.25 nM的selegiline或1µM的1- r-氨基丁酸处理2天。然后用PBS洗涤细胞，用4%多聚甲醛PBS固定。再次用PBS洗涤载玻片，通过在DNA的缺口端添加荧光素12-dUTP来检测凋亡细胞中的片段DNA（原位细胞死亡检测试剂盒，Roche）。载玻片37℃黑暗孵育1 h， PBS洗涤3次，荧光显微镜下观察。绿色荧光与DNA断裂相关。实验重复三次，测定tunel阳性细胞百分比。

Animal/Disease Models: (PLP)-α-synuclein transgenic mice over 6 months of age[3]
Doses: Low-(0.8 mg/kg bw) and high dose (2.5 mg/kg bw)
Route of Administration: Administered subcutaneously (sc) every 24 h for a total period of 4 weeks (from day 1 till day 28 of the experiment).
Experimental Results: Low dose treatment did not show protective efficacy in striatum with number of neurons similar to placebo treated MSA mice. High dose was associated with about 15% rescue of DARPP-32 immunoreactive striatal neurons. Low dose treatment had no effect on nigral neuronal loss, but high dose completely protected nigral neurons with numbers comparable to healthy controls.

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Determination of inhibition of MAO activity in vivo [1]
In in vivo studies, drugs were administered orally by gavage (p.o.). The animals weighed 250 – 300 g at the time of killing. For estimation of in vivo inhibitory effect, varying doses of the inhibitors were administered to groups of five or six rats for the stated times, the animals were killed by decapitation, tissues removed and frozen at −20°C, and enzyme activity determined subsequently as above. Enzyme activity in drug-treated tissues were expressed as a percentage of that in control tissues.

Absorption, Distribution and Excretion
Rasagiline is rapidly absorbed following oral administration. The absolute bioavailability of rasagiline is about 36%.
Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway. After oral administration of 14C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted as unchanged drug in urine.
87 L
After oral administration of (14)C-labeled rasagiline, elimination occurred primarily via urine and secondarily via feces (62% of total dose in urine and 7% of total dose in feces over 7 days), with a total calculated recovery of 84% of the dose over a period of 38 days. Less than 1% of rasagiline was excreted as unchanged drug in urine.
Rasagiline is rapidly absorbed; following oral administration, peak plasma concentrations are achieved in approximately 1 hour. The absolute bioavailability of rasagiline is about 36%. Following administration with a high-fat meal, peak plasma rasagiline concentrations and area under the plasma concentration-time curve (AUC) decreased by approximately 60 and 20%, respectively; because AUC is not substantially affected, rasagiline may be administered with or without food. Rasagiline readily crosses the blood-brain barrier. The mean steady-state or terminal half-life of rasagiline is 31 or 1.342 hours, respectively; however, there is no correlation between rasagiline's pharmacokinetic profile and its pharmacologic effects because the drug irreversibly inhibits MAO-B, and restoration of normal enzyme activity depends on the rate of de novo enzyme synthesis. Rasagiline is approximately 88-94% bound to plasma proteins, with 61-63% bound to albumin.
IV studies in rats and dogs show that the volume of distribution (Vd) of rasagiline is several times that of total body water, indicating extensive tissue distribution. Tissue distribution of (14)C-rasagiline was studied in albino and pigmented rats, revealing peaks of tissue radioactivity between 0.25 and 0.5 hours. Distribution to large intestine, urinary bladder and lacrimal glands takes longer, whilst persistence (up to 24 hrs) was seen in eyes, skin and arterial walls of pigmented animals. In-vitro protein binding in plasma of animals is in the range of 70 to 90% and in human plasma in the range of 88 to 94%.
Oral studies with (14)C-rasagiline show that absorption is rapid in all species, with Cmax attained in less than 2 hours. Absolute bioavailability has been estimated as 53-69% in rats, 13-22% in dogs, and 36% in humans. Toxicokinetic analyses during the toxicology studies showed that exposure was linear at doses higher than the pharmacological selectivity for inhibition of MOA-B and was maintained up to about 5 mg/kg/day. However, kinetics became non-linear at higher doses, possibly indicating saturation of the elimination processes for both rasagiline and its metabolite aminoindan. Accumulation was seen only at the highest doses in the mouse and dog studies (60 and 21 mg/kg/day respectively).
For more Absorption, Distribution and Excretion (Complete) data for RASAGILINE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism.
Rasagiline is extensively metabolized in the liver following oral administration. In vitro studies have shown that CYP1A2 is the predominant P450 isoform involved in the metabolic elimination of rasagiline. The primary human plasma metabolite formed following biotransformation of rasagiline is aminoindan. The proposed principal biotransformation pathways of rasagiline in human are N-dealkylation, hydroxylation of the indan ring, along with Phase II N or O-conjugation, including N-glucuronidation of the parent drug and of its metabolites. There was no bioconversion of rasagiline mesylate (R enantiomer) to its S enantiomer within the human body, as determined in plasma samples for healthy volunteers dosed with rasagiline. Rasagiline is not metabolized to amphetamine or methamphetamine.
An extensive first pass metabolism effect is evident, likely due to rasagiline binding to MAO sites in the intestine prior to passing the liver. Metabolism is rapid and extensive, with a similar profile in all tested species. The primary route of biotransformation is via N-dealkylation to form aminoindan and by hydroxylation to form 3-hydroxy-N-propargyl-1-aminoindan. Conjugation by sulfide or glucuronic acid occurs. Microsomal studies indicate CYP1A2 as the primary metabolising isotype, but rasagiline is neither an inducer nor inhibitor of cytochrome p450. The metabolism of rasagiline under inhibition, induction of CYP1A2 or in presence of concomitant substrate to the enzyme has been addressed clinically.
Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. The metabolism of rasagiline proceeds through two main pathways: N-dealkylation and/or hydroxylation to yield 1-aminoindan (AI), 3-hydroxy-N-propargyl-1 aminoindan (3-OH-PAI) and 3-hydroxy-1-aminoindan (3-OH-AI). In vitro experiments indicate that both routes of rasagiline metabolism are dependent on the cytochrome P450 (CYP) system, with CYP 1A2 being the major isoenzyme involved in rasagiline metabolism. Glucuronide conjugation of rasagiline and its metabolites, with subsequent urinary excretion, is the major elimination pathway.

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Biological Half-Life
Rasagiline has a mean steady-state half life of 3 hours but there is no correlation of pharmacokinetics with its pharmacological effect because of its irreversible inhibition of MAO-B.
Rasagiline's mean steady-state half life is 3 hours ... .
Rasagiline is eliminated with a half life of about 0.6 - 2 hours and ranging from 0.3 to 3.5 hours across the 0.5 to 20 mg dose range examined following oral administration.

Hepatotoxicity
Rasagiline has been reported to cause serum enzyme elevations in a small proportion of patients treated long term, although the abnormalities were usually mild and self-limiting. Rasagiline has not been implicated in cases of acute liver injury, but such instances have been reported with other less specific MAO inhibitors.
Likelihood score: E (unlikely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No clinical use of rasagiline during breastfeeding has been reported. Rasagiline might reduce serum prolactin and interfere with milk production. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Animal studies show that rasagiline reduces serum prolactin. The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
Plasma protein binding ranges from 88-94% with mean extent of binding of 61-63% to human albumin over the concentration range of 1-100 ng/ml.

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Interactions
Antidepressant Agents, Selective Serotonin-reuptake Inhibitors (SSRIs): Potential pharmacologic interaction resembling serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability with rapid vital sign fluctuations, and mental status changes that may progress to extreme agitation, delirium, coma, and death). Concomitant use generally should be avoided. At least 14 days should elapse between discontinuance of rasagiline and initiation of an SSRI.Because both fluoxetine and its principal metabolite have relatively long half-lives, the manufacturer of rasagiline recommends that at least 5 weeks (or longer with high-dose or long-term fluoxetine therapy) elapse between discontinuance of fluoxetine therapy and initiation of rasagiline.
Inhibitors of CYP1A2: Pharmacokinetic interaction observed during concomitant use with ciprofloxacin (increased plasma rasagiline concentrations). Dosage of rasagiline should be limited ... in patients receiving the drug concomitantly with ciprofloxacin or other CYP1A2 inhibitors.
St. John's wort (Hypericum perforatum): Concomitant use is contraindicated.
Potential pharmacologic interaction (resembling serotonin syndrome) with meperidine (coma, severe hypertension or hypotension, severe respiratory depression, seizures, malignant hyperpyrexia, excitation, peripheral vascular collapse, and death). Concomitant use with meperidine, methadone, propoxyphene, or tramadol is contraindicated. At least 14 days should elapse between discontinuance of rasagiline and initiation of meperidine.
For more Interactions (Complete) data for RASAGILINE (12 total), please visit the HSDB record page.

[1]. Rasagiline [N-propargyl-1R(+)-aminoindan] a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol. 2001 Jan;132(2):500-6.

[2]. Comparative neuroprotective effects of Rasagiline and aminoindan with selegiline on dexamethasone-induced brain cell apoptosis. Neurotox Res. 2009 Apr;15(3):284-90.

[3]. Rasagiline is neuroprotective in a transgenic model of multiple system atrophy. Exp Neurol. 2008 Apr;210(2):421-7.

Drug Indication
Azilect is indicated for the treatment of idiopathic Parkinson's disease (PD) as monotherapy (without levodopa) or as adjunct therapy (with levodopa) in patients with end-of-dose fluctuations.

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The present study has demonstrated that rasagiline, like selegiline, is an irreversible inhibitor of MAO-B. This was demonstrated in experiments where rasagiline MAO inhibitory activity was examined in vitro and in vivo when it was given p.o. and MAO-A and -B were then estimated ex vivo in various tissues, at time intervals up to 13 days after rasagiline treatment. It is apparent that rasagiline is a very potent selective MAO-B inhibitor and has a good uptake across the blood-brain barrier, as shown by the similarity of inhibition curves between liver and brain. Although when compared in vitro, rasagiline had similar potency to selegiline for inhibition of MAO-B, the in vivo study showed a greater potency of rasagiline. This greater potency of rasagiline is even more marked if, instead of 50% enzyme inhibition, the dose required for 80% inhibition is measured. The reason for this is not currently known, but may be due to different rates of metabolism of the parent compounds in vivo, or to improved tissue penetration of rasagiline. Interestingly, preliminary studies in humans show an approximately 5 fold greater potency for rasagiline over selegiline for inhibition of platelet MAO-B (unpublished data). Although rasagiline has a greater potency than selegiline, its selectivity for MAO-A and -B inhibition is very similar to what has been reported for selegiline. However, in contrast to selegiline which does not show selectivity between its optical isomers for inhibition of MAO-A and -B, AGN 1135 shows roughly 4 and 2 orders of magnitude between its optical isomers for inhibition of MAO-B and -A respectively. The present results complement findings in non-human primate (monkey) brains (Gotz et al., 1998) where rasagiline was given chronically for 7 days at various doses and MAO-A and -B activities were measured in several brain regions, including caudate nucleus, globus pallidus, cerebral cortex and hippocampus. Rasagiline was shown to be a potent selective inhibitor of MAO-B in the caudate nucleus and globus pallidus where the activity of MAO-B is 4 fold higher than that of MAO-A (Gotz et al., 1998). The recovery of the MAO-A and -B activities after in vivo inhibition, which is related to the synthesis of enzyme apoprotein, differs between the tissues (liver, intestine and brain) examined. The small intestine MAO-B activity has the fastest recovery, while the brain MAO-B activity shows the slowest recovery. These differences in rat tissue enzyme activity recovery after rasagiline treatment, are not unusual since similar findings have been reported for enzyme recovery after inhibition by selegiline and clorgyline (Neff & Goridis, 1972; Della Corte & Tipton, 1980). Indeed, in primate (monkeys and human) brains the half-life for recovery of MAO-B after selegiline treatment has been reported to be well over 30 days (Fowler et al., 1994), and for the rat brain 13 days (Neff & Goridis, 1972; Della Corte & Tipton, 1980). In conclusion, the present study has shown that rasagiline is a potent irreversible inhibitor of MAO-B and it is 3 – 15 times more potent than selegiline in the rat in vivo with a similar selectivity for inhibition of MAO-B to MAO-A. Because of its cleaner pharacological profile, with absence of amphetamine-like properties, formation of the metabolite aminoindan rather than 1-methamphetamine, and recently described neuroprotective and antiapoptotic properties (Finberg et al., 1998; Huang et al., 1999; Youdim et al., 1999), we can conclude that this drug may have a preferential activity to that of selegiline in the treatment of Parkinson's disease.[1]

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We report here for the first time that rasagiline, selegiline, and 1-R-aminoindan significantly prevent dexamethasone-induced brain cell death involving in both neuroblastoma and glioblastoma cells. Among the three compounds, rasagiline has the highest neuroprotective effect compared to either selegiline or 1-R-aminoindan. Rasagiline (Azilect) and selegiline (1-deprenyl or Emsam) are irreversible inhibitors of MAO B. The greater neuroprotective quality of rasagiline may in part be due to the effects of the parent compound and its major metabolite, 1-R-aminoindan. Furthermore, the inhibitory effects of these drugs on MAO B catalytic activity and on apoptotic DNA fragment damage (observed by TUNEL staining) were examined. Rasagiline has shown the highest inhibition on MAO B enzymatic activity (Youdim et al. 2001a) and also has shown the highest prevention on apoptosis compared to selegiline and 1-R-aminoindan. The mechanism by which rasagiline and selegiline initiate their anti-apoptotic effect can be summarized by their up regulation of anti-apoptotic Bcl-2 and Bcl-Xl and down regulation of propaoptotic Bad, Bax, PARP, and caspase 3 (see Youdim et al. 2005a) and Youdim et al. 2006) for reviews). Because Bcl-2 and caspase 3 are key factors for preventing or mediating the mitochondrial-involved apoptosis (Lakhani et al. 2006), it suggests that the MAO inhibitors may protect cells from apoptosis through a mechanism involving the maintenance of mitochondrial homeostasis (Malorni et al. 1998). In addition, structure activity studies with rasagiline have shown that it is propargylamine moiety that produces this effect, since propargylamine which has little or no MAO inhibitory activity has a similar mechanism of neuroprotective activity with similar potency (Bar-Am et al. 2005). Furthermore, both rasagiline and proppargylamine activate neuroprotective protein kinase C (PKCα and PKCε), while down-regulating propaoptotic PKCδ and γ. Inhibition of PKC by GF109203X prevents their neuroprotective activity (Weinreb et al. 2005; Youdim et al. 2005a). The mechanism by which aminoindan has been fully elucidated. The neuroprotective properties of 1-R-aminoindan have been assessed employing a cytotoxic model of human neuroblastoma SKN-SH cells in high-density culture-induced neuronal death and in response to 6-hydroxydopamine. We show that 1-R-aminoindan (0.1–1 µM) significantly reduced the apoptosis-associated phosphorylated protein, H2A.X (Ser139), decreased the cleavage of caspase 9 and caspase 3, while increasing the anti-apoptotic proteins, Bcl-2 and Bcl-xl. Protein kinase C (PKC) inhibitor, GF109203X, prevented the neuroprotection, indicating the involvement of PKC in aminoindan-induced cell survival. Aminoindan markedly elevated pPKC (pan) and specifically that of the pro-survival PKC isoform, PKC epsilon (Bar-Am et al. 2007). In summary, the neurorptoective activity seen with rasagiline and its major metabolite, 1-R-aminoindan in the present and previous studies, may have relevance to the recent prospective clinical study in Parkinsonian subjects, ADAGIO, where rasagiline indicated that early treatment with rasagiline provided benefits that were not obtained with later initiation of the drug. This is the first time that a prospective large-scale, randomized, double-blind trial has provided evidence that a drug might slow down PD progression via neuroprotection (Hughes 2008).[2]

C12H13N.CH4O3S

267.34

267.092

C, 58.40; H, 6.41; N, 5.24; O, 17.95; S, 11.99

161735-79-1

Rasagiline;136236-51-6;Rasagiline-13C3 mesylate;1391052-18-8;Rasagiline-13C3 mesylate racemic;1216757-55-9

3052775

White to off-white solid powder

1.05 g/cm3

305.5ºC at 760 mmHg

155-158°C

146.8ºC

0.000816mmHg at 25°C

2.872

74.78

2

4

2

18

305

1

CS(=O)(=O)O.C#CCN[C@@H]1CCC2=CC=CC=C12

JDBJJCWRXSVHOQ-UTONKHPSSA-N

InChI=1S/C12H13N.CH4O3S/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;1-5(2,3)4/h1,3-6,12-13H,7-9H2;1H3,(H,2,3,4)/t12-;/m1./s1

methanesulfonic acid;(1R)-N-prop-2-ynyl-2,3-dihydro-1H-inden-1-amine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 100 mg/mL (374.06 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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配方 2 中的溶解度: Saline: 30 mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。