Acetylcholinesterase (AChE) (IC50 = 4150 ± 160 nM against erythrocyte-derived AChE)[1]
Butyrylcholinesterase (BChE) (IC50 = 37 ± 5 nM)[1]
Cholinesterase inhibitor (Acetylcholinesterase and Butyrylcholinesterase)[2]

Rivastigmine (S-rivastigmine; 1 µM; 24 hours) coupled with carbachol (10 µM) reduced LPS (2.5 µg/ml)-induced TNF-α and IL-6 by 50% and 46%, respectively. % without making any substantial impact. Pro-inflammatory cytokines are lowered [3]. Rivastigmine (1 µM), carbachol (10 µM), or a combination of both medications show no cytotoxic effects on activated cells [3].

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Rivastigmine was evaluated for its inhibitory activity against human erythrocyte-derived acetylcholinesterase (AChE) and plasma-derived butyrylcholinesterase (BChE) ex vivo. The IC50 values were determined to be 4150 ± 160 nM for AChE and 37 ± 5 nM for BChE.[1]
This indicates that Rivastigmine is a more potent inhibitor of BChE than of AChE (approximately 112-fold selective for BChE based on the reported IC50 values).[1]
The literature notes that Rivastigmine is unusual because its activity against brain-derived AChE is far more potent than against erythrocyte-derived AChE. Therefore, the measured IC50 value against erythrocyte-derived AChE dramatically underestimates its activity in the brain. The agent has been reported to be nonselective between AChE and BChE when considering brain activity.[1]

An intraperitoneal injection of rivastigmine (S-rivastigmine; 0.5-2.5 mg/kg; administered 60 minutes prior to testing) markedly and dose-dependently alleviated behavioral abnormalities caused by aluminum [4]. In BALB/c OlaHsd male 8–9 week old mice weighing 200–250 grams with acute colitis, rivastigmine (0.5, 1 mg/kg/day; SC; for 8 days) decreases IL-6 concentrations by roughly 50% and 60%, respectively, but not TNF-α and IL-1β concentrations [3]. At 1 mg/kg, rivastigmine totally stopped bleeding and inhibited colonic contractions, but not at 0.5 mg/kg. While rivastigmine (1 mg/kg) reduced submucosal edema and cellular infiltration, treatment with rivastigmine (0.5 mg/kg) showed minimal change in these pathological findings. Additionally, partial recovery of the crypt architecture was observed. At the conclusion of the trial, a 4.7% weight reduction was achieved with rivastigmine (1 mg/kg) [3].

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This clinical study evaluated the efficacy of switching patients with probable Alzheimer's disease from oral cholinesterase inhibitors to the rivastigmine transdermal patch. After 24 weeks of treatment, 82.8% (96 out of 116) of the patients demonstrated either an improvement or no further deterioration in global functioning, as assessed by the Clinical Global Impression of Change (CGIC) score.[2]
Regarding cognitive function assessed by the Korean version of the Mini-Mental State Examination (K-MMSE), 64.3% of the 116 patients showed an increase or stabilization in score from baseline at week 24. However, the mean change in K-MMSE score (0.42 ± 0.8) was not statistically significant (p > 0.05).[2]
No statistically significant changes from baseline were observed in the Korean Instrumental Activities of Daily Living (K-IADL) and Clinical Dementia Rating-Sum of Box (CDR-SB) scores at week 24.[2]

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)

Absorption, Distribution and Excretion
Rivasidine is extensively metabolized to the decarbamoyl metabolite NAP226-90 via cholinesterase-mediated hydrolysis. The main elimination route is renal excretion. Less than 1% of the administered dose is excreted in feces. 1.8 to 2.7 L/kg Renal clearance = 2.1–2.8 L/hr Metabolism/Metabolite Rivasidine is rapidly metabolized via cholinesterase-mediated hydrolysis. Biological Half-Life 1.5 hours Rivasidine Transdermal patches deliver the drug directly into the bloodstream through the skin, thus avoiding the first-pass effect that occurs with oral administration. [2]

Hepatotoxicity
In large placebo-controlled trials, rivastigmine treatment did not increase the incidence of elevated serum enzymes or report any clinically significant liver injury with jaundice compared to placebo. However, since the introduction of rivastigmine (transdermal patch) into the clinical market, at least one case has been reported as being associated with clinically significant hepatotoxicity and mild jaundice. This case occurred 2 months prior, with elevated serum enzymes showing mild hepatocellular changes. The patient also presented with a mild rash and eosinophilia, but no autoimmune features. Complete recovery occurred within 5 weeks of discontinuation of the drug. Probability score: D (likely a rare cause of clinically significant drug-induced liver injury). Protein binding 40% In this 24-week study, 12.2% (20 out of 164 enrolled patients) discontinued the study due to adverse events. The most common adverse event was skin damage at the application site, such as erythema or pruritus, with an incidence of 11%. No serious skin problems were reported. [2]
1.2% of patients reported gastrointestinal problems (e.g., nausea, vomiting, anorexia). [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.

Rivasidamine is a carbamate formed by the condensation of the carboxyl group of ethyl (methyl)carbamate with the phenolic hydroxyl group of 3-[(1S)-1-(dimethylamino)ethyl]phenol. It is a reversible cholinesterase inhibitor with dual action as an EC 3.1.1.8 (cholinesterase) inhibitor, neuroprotective agent, and cholinergic drug. It is a carbamate and tertiary amine compound, the conjugate base of rivasidamine (1+). Rivasidamine is a parasympathomimetic or cholinergic drug used to treat mild to moderate Alzheimer's disease-related dementia. Rivasidamine is a cholinesterase inhibitor that simultaneously inhibits butyrylcholinesterase and acetylcholinesterase. The mechanism of action of rivasidamine is as a cholinesterase inhibitor. Rivasidamine is an oral acetylcholinesterase inhibitor used to treat Alzheimer's disease. The incidence of serum enzyme elevation during rivasidamine treatment is extremely low, and it rarely causes clinically significant liver damage.
Livastimin is a carbamate reversible cholinesterase inhibitor with central nervous system selectivity, used to treat dementia associated with Alzheimer's disease and Parkinson's disease.
See also: Livastimin tartrate (narrow spectrum).

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Drug Indications
For the treatment of mild to moderate dementia associated with Parkinson's disease or Alzheimer's disease.
FDA Label
For the treatment of symptoms of mild to moderate Alzheimer's disease dementia. For symptomatic treatment of patients with idiopathic Parkinson's disease and mild to moderate dementia. For symptomatic treatment of patients with idiopathic Parkinson's disease and mild to moderate dementia. For symptomatic treatment of patients with idiopathic Parkinson's disease and mild to moderate dementia. For symptomatic treatment of patients with idiopathic Parkinson's disease and mild to moderate dementia. Symptomatic treatment for patients with idiopathic Parkinson's disease and mild to moderate dementia. (This phrase is repeated 6 times in the original text.) Symptomatic treatment for mild to moderate dementia in patients with idiopathic Parkinson's disease.
Treatment of Dementia
Treatment of Dementia

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Mechanism of Action
Rivastin is a carbamate derivative whose structure is related to physostigmine but not donepezil or tacrine. The exact mechanism of action of rivastin is not fully understood, but studies have shown that rivastin reversibly binds to and inactivates cholinesterases (e.g., acetylcholinesterase, butyrylcholinesterase), thereby preventing the hydrolysis of acetylcholine and leading to an increase in acetylcholine concentration at cholinergic synapses. Compared to peripheral tissues, rivastin exhibits relative specificity for the anticholinesterase activity of acetylcholinesterase and butyrylcholinesterase in the brain.

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Pharmacodynamics
Rivastin is a parasympathomimetic drug and a reversible cholinesterase inhibitor. One of the early pathophysiological features of Alzheimer's disease is acetylcholine deficiency, which is closely associated with memory loss and cognitive impairment. Acetylcholine deficiency is caused by the selective loss of cholinergic neurons in the cerebral cortex, basal ganglia, and hippocampus. Tacrine is thought to exert its therapeutic effect by enhancing cholinergic function. Although the exact mechanism of action of livasidamine is unclear, it is presumed that it also exerts its therapeutic effect by enhancing cholinergic function. This is achieved by reversibly inhibiting the hydrolysis of acetylcholine by cholinesterase, thereby increasing the concentration of acetylcholine. If this mechanism is correct, the efficacy of livasidamine may diminish as the disease progresses and the number of functional cholinergic neurons decreases. Livasidamine is one of the compounds currently undergoing clinical evaluation or approved by the FDA for the treatment of Alzheimer's disease. [1]
Livasidamine has much stronger activity against brain-derived acetylcholinesterase (AChE) than against erythrocyte-derived AChE, and therefore its IC50 value for the latter significantly underestimates its activity against the brain. [1]
Livasidamine has been reported to have no selectivity for AChE and butyrylcholinesterase (BChE) in terms of its activity in the brain. [1]
Livasidamine is a cholinesterase inhibitor used to treat symptoms of mild to moderate Alzheimer's disease. This study investigated livasidamine transdermal patches as an alternative therapy for patients who do not respond well to or are intolerant of oral cholinesterase inhibitors (donepezil, galantamine, or livasidamine capsules). [2] Transdermal patches are designed to provide a smooth and sustained drug release, which may improve tolerability compared to oral formulations. [2] The study concluded that for suspected Alzheimer's patients, switching from oral cholinesterase inhibitors to rivastigmine transdermal patches can be done immediately without a discontinuation period, and is safe and well-tolerated. [2] The starting dose is a 5 cm² patch, which can be increased to a 10 cm² patch after 4 weeks depending on tolerance. The patch is applied to the upper back daily for 24 hours. [2]

C14H22N2O2

250.34

250.168

123441-03-2

Rivastigmine tartrate;129101-54-8;(rac)-Rivastigmine-d6;194930-04-6

77991

Colorless to light yellow liquid

1.0±0.1 g/cm3

316.2±34.0 °C at 760 mmHg

145.0±25.7 °C

0.0±0.7 mmHg at 25°C

1.518

2.14

0

3

5

18

269

1

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

XSVMFMHYUFZWBK-NSHDSACASA-N

InChI=1S/C14H22N2O2/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4/h7-11H,6H2,1-5H3/t11-/m0/s1

[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

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

DMSO : ≥ 50 mg/mL (~199.73 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.99 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.99 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.99 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)