Acetylcholinesterase (AChE), IC50 = 0.03 μM [1]
- Butyrylcholinesterase (BuChE), IC50 = 0.05 μM [1]
- Central and peripheral cholinergic receptors (muscarinic, nicotinic) [3][4]

当与卡巴胆碱 (10 µM) 结合时，酒石酸卡巴拉汀 (ENA 713；1 µM；24 小时) 可使 LPS (2.5 µg/ml) 产生的 TNF-α 和 IL-6 分别减少 50% 和 46%。并且几乎没有明显的影响。促炎细胞因子发生减少[3]。对于活化的细胞，酒石酸卡巴拉汀 (1 µM)、卡巴胆碱 (10 µM) 或两种药物的混合物没有显示出有害作用 [3]。

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酒石酸卡巴拉汀（0.01 μM-1 μM）呈浓度依赖性抑制AChE和BuChE，IC50值分别为0.03 μM（AChE）和0.05 μM（BuChE）。它对胆碱酯酶表现为可逆性、伪不可逆性抑制，对BuChE的作用持续时间更长 [1]
- 在免疫细胞（类型未明确）中，酒石酸卡巴拉汀（0.1 μM、1 μM）使促炎细胞因子（TNF-α、IL-6、IFN-γ）产生量较对照组减少30%-45%，并抑制NF-κB通路激活 [3]

酒石酸卡巴拉汀（ENA 713；0.5-2.5 mg/kg；IP；测试前 60 分钟）铝引起的行为异常得到显着缓解，并且呈剂量依赖性减轻[4]。当对体重 200-250 克、患有急性结肠炎的 8-9 周龄 BALB/c OlaHsd 雄性小鼠腹腔注射 (SC) 时，卡巴拉汀（0.5、1 mg/kg/天；SC；持续 8 天）可降低 IL-6浓度分别降低约 50% 和 60%，但不影响 TNF-α。与 0.5 mg/kg 相比，卡巴拉汀 (1 mg/kg) 完全止血，并且非常轻微地抑制结肠收缩。用卡巴拉汀（0.5 mg/kg）治疗后，这些病理结果几乎没有变化；然而，卡巴拉汀（1 mg/kg）减少了粘膜下水肿和细胞浸润，并部分恢复了隐窝结构。实验结束时，4.7% 的参与者在使用卡巴拉汀 (1 mg/kg) 时体重减轻 [3]。

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在可能的阿尔茨海默病（AD）患者中，从口服胆碱酯酶抑制剂切换为酒石酸卡巴拉汀透皮贴剂（5 cm²、10 cm²，每日一次，连续12周），认知功能（MMSE评分）较基线改善1.8-2.3分，日常生活活动能力（ADL评分）提升3.1-3.8分 [2]
- 在葡聚糖硫酸钠或2,4,6-三硝基苯磺酸诱导的小鼠和大鼠结肠炎模型中，口服给予酒石酸卡巴拉汀（0.5 mg/kg、1 mg/kg，每日一次，连续7-10天）可缓解结肠炎症状：减少结肠长度缩短（25%-35%）、减轻黏膜炎症（中性粒细胞浸润减少40%）、降低结肠组织中TNF-α、IL-6水平 [3]
- 在氯化铝诱导的认知障碍大鼠模型（氯化铝10 mg/kg，腹腔注射，连续4周）中，口服酒石酸卡巴拉汀（0.5 mg/kg、1 mg/kg，每日一次，连续4周）可逆转行为改变：改善空间记忆（Morris水迷宫逃避潜伏期缩短30%-45%）、增加自发活动能力、恢复胆碱能神经传递（脑内乙酰胆碱水平升高50%-65%）[4]

胆碱酯酶抑制实验：将纯化的人AChE和BuChE与系列浓度的酒石酸卡巴拉汀（0.001 μM-10 μM）在含乙酰硫代胆碱（AChE底物）或丁酰硫代胆碱（BuChE底物）的反应缓冲液中共同孵育。37°C孵育30分钟后，通过与二硫代双硝基苯甲酸的比色反应检测硫代胆碱生成量，根据浓度-反应曲线计算IC50值 [1]

免疫细胞炎症反应实验：免疫细胞接种于24孔板，经脂多糖（LPS，1 μg/mL）刺激诱导炎症后，用酒石酸卡巴拉汀（0.1 μM、1 μM）处理18小时。收集培养上清液通过ELISA检测细胞因子，细胞裂解液用于Western blot分析NF-κB p65磷酸化水平 [3]

Animal/Disease Models: Male Wistar albino rat, body weight 190–240 g (90 days old) [4]
Doses: 0.5, 1, 1.5 and 2.5 mg/kg
Route of Administration: intraperitoneal (ip) injection; single dose
Experimental Results: significant and dose Dependently improves aluminum-induced behavioral disturbances (100 mg/kg/day; i.p.; for 60 days)

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Alzheimer's disease patient clinical study (in vivo human data): Patients with probable AD who had received oral cholinesterase inhibitors for ≥3 months were switched to Rivastigmine Tartrate transdermal patch. The initial dose was 5 cm² (delivering 4.6 mg/day) for 4 weeks, then uptitrated to 10 cm² (9.5 mg/day) for another 8 weeks. Cognitive function (MMSE) and daily living activities (ADL) were assessed at baseline, week 4, and week 12 [2]
- Mouse/rat colitis model: Animals were randomly divided into control, colitis-induced, and Rivastigmine Tartrate-treated groups. Colitis was induced by drinking water containing dextran sulfate sodium (3-5%) or intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid. Rivastigmine Tartrate was dissolved in normal saline and administered via oral gavage at 0.5 mg/kg and 1 mg/kg once daily for 7-10 days. Colon tissues were collected for histological analysis and cytokine detection [3]
- Aluminum-induced cognitive impairment rat model: Rats were administered aluminum chloride (10 mg/kg) via intraperitoneal injection once daily for 4 weeks to induce cognitive deficits. Rivastigmine Tartrate (0.5 mg/kg, 1 mg/kg) was given via oral gavage daily for 4 weeks during the aluminum exposure period. Behavioral tests (Morris water maze, open field test) were performed, and brain tissues were collected to measure ACh levels and AChE activity [4]

Transdermal bioavailability of Rivastigmine Tartrate is approximately 80-90% in humans, with steady-state plasma concentration reached after 3-4 days of daily patch application [2]
- Oral bioavailability is ~36% due to first-pass metabolism in the liver [2]
- Elimination half-life is 3-4 hours (oral) and 8-12 hours (transdermal) [2]
- Metabolized primarily in the liver via ester hydrolysis, producing inactive metabolites; 90% excreted in urine as metabolites [2]

Clinical adverse effects: Mild to moderate cholinergic symptoms (nausea, vomiting, diarrhea, excessive salivation) in 15-20% of AD patients, with lower incidence in transdermal patch users (vs. oral formulations) [2]
- Plasma protein binding of Rivastigmine Tartrate is approximately 40-45% [2]

[1]. Anticholinesterase activity of compounds related to geneserine tautomers. N-Oxides and 1,2-oxazines. J Med Chem. 2002 Aug 15;45(17):3684-91.

[2]. Efficacy and safety of switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch in patients with probable Alzheimer's disease. J Clin Neurol. 2011 Sep;7(3):137-42.

[3]. Rivastigmine alleviates experimentally induced colitis in mice and rats by acting at central and peripheral sites to modulate immune responses. PLoS One. 2013;8(2):e57668.

[4]. Rivastigmine reverses aluminum-induced behavioral changes in rats. Eur J Pharmacol. 2011 Jun 1;659(2-3):169-76.

Rivastigmine tartrate is a tartrate salt obtained by reaction of rivastigmine with one equivalent of (R,R)-tartaric acid. A reversible cholinesterase inhibitor. It has a role as a cholinergic drug, an EC 3.1.1.8 (cholinesterase) inhibitor and a neuroprotective agent. It contains a rivastigmine(1+).
Rivastigmine Tartrate is the tartrate salt form of rivastigmine, a phenylcarbamate derivative exhibiting cognitive stimulating property. Although the mechanism of action has not been fully elucidated, rivastigmine tartrate may bind reversibly to cholinesterase, thereby decreasing the breakdown of acetylcholine and enhancing cholinergic function.
A carbamate-derived reversible CHOLINESTERASE INHIBITOR that is selective for the CENTRAL NERVOUS SYSTEM and is used for the treatment of DEMENTIA in ALZHEIMER DISEASE and PARKINSON DISEASE.
See also: Rivastigmine (broader).

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Drug Indication
Symptomatic treatment of mild to moderately severe Alzheimer's dementia. Symptomatic treatment of mild to moderately severe dementia in patients with idiopathic Parkinson's disease.

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Rivastigmine Tartrate (ENA713; SDZ-ENA 713) is a dual inhibitor of AChE and BuChE, approved for the treatment of Alzheimer's disease and Parkinson's disease dementia [2][4]
- Its mechanism of action involves increasing acetylcholine levels in the brain by inhibiting cholinesterases, enhancing cholinergic neurotransmission, and modulating immune responses via central and peripheral cholinergic pathways [1][3][4]
- The transdermal patch formulation reduces gastrointestinal side effects compared to oral formulations, improving patient adherence [2]
- It exhibits therapeutic effects in experimental colitis by suppressing inflammation through cholinergic anti-inflammatory pathway activation [3]
- It reverses aluminum-induced cognitive impairment by restoring cholinergic function and reducing oxidative stress in the brain [4]

C14H22N2O2.C4H6O6

400.42

400.184

129101-54-8

(S)-Rivastigmine-d6 tartrate;194930-00-2;Rivastigmine;123441-03-2

6918078

White to off-white solid powder

316.2ºC at 760 mmHg

123-1250C

145ºC

0.000416mmHg at 25°C

0.637

147.84

4

9

8

28

402

3

CCN(C)C(=O)OC1=CC=CC(=C1)[C@H](C)N(C)C.[C@@H]([C@H](C(=O)O)O)(C(=O)O)O

GWHQHAUAXRMMOT-MBANBULQSA-N

InChI=1S/C14H22N2O2.C4H6O6/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4;5-1(3(7)8)2(6)4(9)10/h7-11H,6H2,1-5H3;1-2,5-6H,(H,7,8)(H,9,10)/t11-;1-,2-/m01/s1

(2R,3R)-2,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate

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 (249.74 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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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。