| Size | Price | |
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| Other Sizes |
| Targets |
Rivastigmine metabolite targets acetylcholinesterase (AChE), a key enzyme that breaks down the neurotransmitter acetylcholine (ACh) in the synaptic cleft [16L5-L7, L10-L12, L33-L35]. By inhibiting AChE, it increases the concentration and duration of action of acetylcholine in the brain, thereby enhancing cholinergic neurotransmission. This mechanism of action is thought to improve cognitive function in patients with Alzheimer‘s disease. The metabolite is more potent as an AChE inhibitor than the parent drug rivastigmine.
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| ln Vitro |
As an active metabolite of rivastigmine, this compound is a potent acetylcholinesterase (AChE) inhibitor in biochemical assays. It directly inhibits the enzymatic activity of AChE, preventing the hydrolysis of acetylcholine. The metabolite exhibits a higher potency for AChE compared to the parent drug, making it a key contributor to the overall pharmacological activity of rivastigmine therapy. While specific IC50 values are not provided in the search results, the compound demonstrates potent inhibition in standard AChE assays.
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| ln Vivo |
Rivastigmine metabolite is the major active species responsible for the in vivo efficacy of the parent drug rivastigmine. Following oral administration of rivastigmine, the parent drug is rapidly metabolized in the kidney to this active metabolite, which reaches the brain and potently inhibits AChE. This leads to increased brain acetylcholine levels and produces symptomatic improvements in cognition, function, and behavior in patients with Alzheimer‘s disease and Parkinson's disease dementia. The metabolite‘s activity in vivo supports the clinical effectiveness of rivastigmine.
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| Enzyme Assay |
An AChE inhibition assay can be used to measure the potency of the rivastigmine metabolite. Procedure: Acetylcholinesterase enzyme (e.g., from human or electric eel) is incubated with varying concentrations of rivastigmine metabolite (e.g., 0.001, 0.01, 0.1, 1, 10, 100 microM) in 96-well plates for 15 minutes at 25degC. The substrate, acetylthiocholine (ATCh), and the colorimetric reagent, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB, Ellman‘s reagent), are then added. The enzymatic reaction produces a yellow color (5-thio-2-nitrobenzoate), which is measured by absorbance at 412 nm every 2 minutes for 30 minutes. The rate of absorbance increase is proportional to enzyme activity. The percent inhibition and IC50 are calculated from the dose-response curve.
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| Cell Assay |
The metabolite's effect on cholinergic neurons can be assessed in neuronal cell lines. Procedure: SH-SY5Y human neuroblastoma cells are differentiated into a neuron-like phenotype using retinoic acid. Cells are seeded in 96-well plates and treated with various concentrations of rivastigmine metabolite (e.g., 0.01, 0.1, 1, 10, 100 microM) for 1-24 hours. After treatment, cells are washed, and acetylcholinesterase activity is measured in cell lysates using the Ellman‘s assay (as described in the enzyme assay). The culture medium can also be collected to measure acetylcholine levels by ELISA. Cell viability is assessed using the MTT assay to ensure that observed effects are not due to cytotoxicity.
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| Animal Protocol |
Rivastigmine and its metabolite have been extensively studied in animal models of cognitive impairment. A typical procedure for testing AChE inhibitors: Male Wistar rats or C57BL/6 mice are given rivastigmine metabolite or the parent drug intraperitoneally or orally at doses of 0.1-5 mg/kg. After 1-4 hours, the animals are sacrificed, and the cortex and hippocampus are rapidly dissected. Brain tissue homogenates are prepared, and AChE activity is measured using the Ellman's assay. The level of acetylcholine in the brain is also measured by HPLC or LC-MS/MS. The degree of AChE inhibition and the increase in acetylcholine levels are quantified. The Y-maze or Morris water maze is used to assess improvements in short-term spatial memory.
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| ADME/Pharmacokinetics |
The PK properties of rivastigmine metabolite are derived from the parent drug. Rivastigmine is rapidly and completely absorbed after oral administration and undergoes extensive metabolism primarily in the kidney to the active metabolite NAP 226-90. The metabolite is further metabolized before renal excretion. The parent drug has a short half-life (~1.5 hours), but the metabolite has a slightly longer half-life and is the main contributor to sustained AChE inhibition. The metabolite's oral bioavailability is dependent on the conversion of the parent drug in the kidney. Its high permeability and molecular weight (165 Da) allow it to cross the blood-brain barrier.
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| Toxicity/Toxicokinetics |
The rivastigmine metabolite is derived from an FDA-approved drug and is expected to have a manageable safety profile. The primary mechanism-based toxicity of AChE inhibitors is cholinergic excess, which can cause nausea, vomiting, diarrhea, dizziness, headache, and bradycardia. These adverse effects are dose-limiting and are more common with the parent drug rivastigmine. The metabolite itself is not administered directly; it is produced endogenously. The tolerability of rivastigmine therapy is well established, with most side effects being reversible upon dose reduction or discontinuation.
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| References | |
| Additional Infomation |
Rivastigmine metabolite (NAP 226-90) is the major active metabolite of the carbamate AChE inhibitor rivastigmine, which is used clinically to treat mild to moderate Alzheimer‘s disease and Parkinson's disease dementia [16L10-L12, L24-L25]. Unlike some other AChE inhibitors, rivastigmine acts as a pseudo-irreversible (slowly reversible) inhibitor that covalently carbamylates the active site of the enzyme, leading to a longer duration of action. The metabolite is produced primarily in the kidney through the action of carboxylesterases [16L6-L7, L24, L33-L35]. It is promising for research of Alzheimer's disease and can be used as a standard in analytical studies to monitor rivastigmine pharmacokinetics and metabolism [16L6-L8]. The compound is for research use only and is not intended for human therapeutic administration.
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| Molecular Formula |
C10H15NO
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|---|---|
| Molecular Weight |
165.23
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| Exact Mass |
165.115
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| CAS # |
139306-10-8
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| PubChem CID |
445892
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
241.3±15.0 °C at 760 mmHg
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| Melting Point |
87-88ºC
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| Flash Point |
97.2±19.0 °C
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| Vapour Pressure |
0.0±0.5 mmHg at 25°C
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| Index of Refraction |
1.539
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| LogP |
1.59
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
12
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| Complexity |
136
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O([H])C1=C([H])C([H])=C([H])C(=C1[H])[C@]([H])(C([H])([H])[H])N(C([H])([H])[H])C([H])([H])[H]
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| InChi Key |
GQZXRLWUYONVCP-QMMMGPOBSA-N
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| InChi Code |
InChI=1S/C10H15NO/c1-8(11(2)3)9-5-4-6-10(12)7-9/h4-8,12H,1-3H3/t8-/m0/s1
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| Chemical Name |
3-[(1S)-1-(dimethylamino)ethyl]phenol
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| Synonyms |
NAP 226-90
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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: (1). Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : ≥ 200 mg/mL (~1210.43 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (30.26 mM) (saturation unknown) in 10% DMSO +40% PEG300 +5% Tween-80 +45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution。
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (30.26 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 the 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix well. 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (30.26 mM) (saturation unknown) in 10% DMSO +90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution。 |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 6.0522 mL | 30.2608 mL | 60.5217 mL | |
| 5 mM | 1.2104 mL | 6.0522 mL | 12.1043 mL | |
| 10 mM | 0.6052 mL | 3.0261 mL | 6.0522 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04237805
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