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Purity: ≥98%
Rivastigmine Tartrate (formerly ENA-713, SDZ-ENA 713; Exelon, Exelon Patch), the tartrate salt of rivastigmine, is a potent and reversible cholinesterase inhibitor used to treat mild to moderate dementia caused by Alzheimer's or Parkinson's disease. It inhibits cholinesterase with an IC50 of 5.5 μM, and is used as a parasympathomimetic or cholinergic agent for the management of mild to moderate Alzheimer disease, Dementia, and Parkinson's Disease. Rivastigmine is a carbamate-derived reversible cholinesterase inhibitor that is selective for the central nervous system. It acts by covalently modifying a serine residue in the active site by carbamoylation, as it stabilizes or reduces the rate of decline in certain cognitive functions.
| Targets |
Acetylcholinesterase (AChE), IC50 = 0.03 μM [1]
- Butyrylcholinesterase (BuChE), IC50 = 0.05 μM [1] - Central and peripheral cholinergic receptors (muscarinic, nicotinic) [3][4] |
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| ln Vitro |
When coupled with carbachol (10 µM), rivastigmine tartrate (ENA 713; 1 µM; 24 hours) decreased TNF-α and IL-6 produced by LPS (2.5 µg/ml) by 50% and 46%, respectively. and has little to no noticeable effect. Decreases in pro-inflammatory cytokines occur [3]. On activated cells, rivastigmine tartrate (1 µM), carbachol (10 µM), or a mix of the two medications show no harmful effects [3].
Rivastigmine Tartrate (0.01 μM-1 μM) inhibited AChE and BuChE in a concentration-dependent manner, with IC50 values of 0.03 μM (AChE) and 0.05 μM (BuChE). It exhibited reversible, pseudo-irreversible inhibition of cholinesterases, with a longer duration of action on BuChE [1] - In immune cells (unspecified type), Rivastigmine Tartrate (0.1 μM, 1 μM) reduced the production of proinflammatory cytokines (TNF-α, IL-6, IFN-γ) by 30-45% compared to control, and inhibited NF-κB pathway activation [3] |
| ln Vivo |
Rivastigmine tartrate (ENA 713; 0.5-2.5 mg/kg; IP; 60 minutes before testing) aluminum-induced behavioral abnormalities were considerably and dose-dependently alleviated [4]. When administered intraperitoneally (SC) to BALB/c OlaHsd male mice 8–9 weeks old weighing 200–250 grams and suffering from acute colitis, rivastigmine (0.5, 1 mg/kg/day; SC; for 8 days) decreases IL-6 concentrations by around 50% and 60%, respectively, but does not affect TNF-α. In contrast to 0.5 mg/kg, rivastigmine (1 mg/kg) totally stopped bleeding and very slightly inhibited colonic contractions. Little changed in these pathological findings after treatment with rivastigmine (0.5 mg/kg); however, rivastigmine (1 mg/kg) reduced submucosal edema and cellular infiltration and partially restored the crypt architecture. At the conclusion of the experiment, 4.7% of the participants lost weight when using rivastigmine (1 mg/kg) [3].
In patients with probable Alzheimer's disease (AD) switching from oral cholinesterase inhibitors to Rivastigmine Tartrate transdermal patch (5 cm², 10 cm², once daily for 12 weeks), cognitive function (assessed by MMSE score) improved by 1.8-2.3 points, and daily living activities (ADL score) increased by 3.1-3.8 points compared to baseline [2] - In mouse and rat colitis models (induced by dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid), oral administration of Rivastigmine Tartrate (0.5 mg/kg, 1 mg/kg, once daily for 7-10 days) alleviated colitis symptoms: reduced colon length shortening (by 25-35%), decreased mucosal inflammation (neutrophil infiltration reduced by 40%), and lowered colonic TNF-α, IL-6 levels [3] - In aluminum-induced cognitive impairment rats (aluminum chloride 10 mg/kg, intraperitoneal injection for 4 weeks), oral Rivastigmine Tartrate (0.5 mg/kg, 1 mg/kg, daily for 4 weeks) reversed behavioral changes: improved spatial memory (Morris water maze escape latency reduced by 30-45%), increased locomotor activity, and restored cholinergic neurotransmission (brain ACh levels increased by 50-65%) [4] |
| Enzyme Assay |
Cholinesterase inhibition assay: Purified human AChE and BuChE were incubated with serial concentrations of Rivastigmine Tartrate (0.001 μM-10 μM) in reaction buffer containing acetylthiocholine (AChE substrate) or butyrylthiocholine (BuChE substrate). The reaction was carried out at 37°C for 30 minutes, and thiocholine production was detected via colorimetric reaction with dithio-bis-nitrobenzoic acid. IC50 values were calculated from concentration-response curves [1]
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| Cell Assay |
Immune cell inflammatory response assay: Immune cells were seeded in 24-well plates and stimulated with LPS (1 μg/mL) to induce inflammation, followed by Rivastigmine Tartrate (0.1 μM, 1 μM) treatment for 18 hours. Culture supernatants were collected for cytokine detection via ELISA, and cell lysates were used for Western blot to analyze NF-κB p65 phosphorylation [3]
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| Animal Protocol |
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) 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] |
| ADME/Pharmacokinetics |
The bioavailability of Livas's tartrate transdermal administration is approximately 80-90% in the human body, and steady-state plasma concentrations can be reached after 3-4 days of daily application [2]. - Due to first-pass metabolism in the liver, the oral bioavailability is approximately 36% [2]. - The elimination half-life is 3-4 hours (oral) and 8-12 hours (transdermal) [2]. - It is mainly metabolized in the liver through ester hydrolysis, producing inactive metabolites; 90% is excreted in the urine as metabolites [2].
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| Toxicity/Toxicokinetics |
Clinical adverse reactions: 15-20% of AD patients experience mild to moderate cholinergic symptoms (nausea, vomiting, diarrhea, excessive salivation), with a lower incidence in transdermal patch users (compared to oral formulations) [2]
- The plasma protein binding rate of rivastigmine tartrate is approximately 40-45% [2] |
| References |
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| Additional Infomation |
Rivastigmine tartrate is a tartrate salt prepared by reacting livasmin with an equivalent (R,R)-tartaric acid. It is a reversible cholinesterase inhibitor with the effects of a cholinergic drug, EC 3.1.1.8 (cholinesterase) inhibitor, and neuroprotective agent. It contains the livasmin (1+) ion. Livasmin tartrate is the tartrate form of livasmin, a phenylcarbamate derivative with cognitive stimulant effects. Although its mechanism of action is not fully elucidated, livasmin tartrate may reversibly bind to cholinesterase, thereby reducing the breakdown of acetylcholine and enhancing cholinergic function. Livasmin is a carbamate reversible cholinesterase inhibitor with central nervous system selectivity, used to treat dementia caused by Alzheimer's disease and Parkinson's disease. See also: Livasmin (broadly defined).
Drug Indications> For the treatment of dementia symptoms caused by mild to moderate Alzheimer's disease. For the symptomatic treatment of mild to moderate dementia in patients with idiopathic Parkinson's disease. Livasmidine tartrate (ENA713; SDZ-ENA 713) is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) and has been approved for the treatment of Alzheimer's disease and Parkinson's disease dementia[2][4] - Its mechanism of action includes increasing acetylcholine levels in the brain by inhibiting cholinesterase, enhancing cholinergic neurotransmission, and regulating immune responses through central and peripheral cholinergic pathways[1][3][4] - Transdermal patches reduce gastrointestinal side effects compared to oral formulations, thereby improving patient compliance[2] - It exerts a therapeutic effect in experimental colitis by inhibiting inflammation by activating cholinergic anti-inflammatory pathways[3] - It restores…reverses aluminum-induced cognitive impairment cholinergic function and reduces oxidative stress in the brain[4] |
| Molecular Formula |
C14H22N2O2.C4H6O6
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| Molecular Weight |
400.42
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| Exact Mass |
400.184
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| CAS # |
129101-54-8
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| Related CAS # |
(S)-Rivastigmine-d6 tartrate;194930-00-2;Rivastigmine;123441-03-2
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| PubChem CID |
6918078
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| Appearance |
White to off-white solid powder
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| Boiling Point |
316.2ºC at 760 mmHg
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| Melting Point |
123-1250C
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| Flash Point |
145ºC
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| Vapour Pressure |
0.000416mmHg at 25°C
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| LogP |
0.637
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
28
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| Complexity |
402
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| Defined Atom Stereocenter Count |
3
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| SMILES |
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
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| InChi Key |
GWHQHAUAXRMMOT-MBANBULQSA-N
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| InChi Code |
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
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| Chemical Name |
(2R,3R)-2,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (249.74 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4974 mL | 12.4869 mL | 24.9738 mL | |
| 5 mM | 0.4995 mL | 2.4974 mL | 4.9948 mL | |
| 10 mM | 0.2497 mL | 1.2487 mL | 2.4974 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02063269 | Unknown † | Drug: Rivastigmine | Alzheimer's Disease | Seoul National University Hospital | February 2014 | Not Applicable |
| NCT02703636 | Completed Has Results | Drug: Rivastigmine Patch | Mild to Moderate Alzheimer's Disease | Novartis Pharmaceuticals | May 9, 2016 | Phase 4 |
| NCT00624663 | Completed | Drug: Rivastigmine | Rivastigmine Toxicity | Tel-Aviv Sourasky Medical Center | January 2009 | Not Applicable |
| NCT01073319 | Completed | Other: Placebo Drug: Rivastigmine |
Methamphetamine Dependence Substance Abuse Methamphetamine Abuse |
Baylor College of Medicine | July 2009 | Phase 1 |
| NCT02413554 | Completed | Drug: Rivastigmine patch | Delirium | Chung-Ang University Hosptial, Chung-Ang University College of Medicine |
April 2013 | Phase 4 |
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