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| 5mg |
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| 10mg |
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| Targets |
The primary target of Ambenonium chloride is acetylcholinesterase (AChE). It inhibits AChE in a rapidly reversible, non-covalent manner with extremely high affinity. It shows strong inhibition of human AChE with an inhibition constant Ki of 0.12 nM and an IC₅₀ of 0.7 nM. It also inhibits butyrylcholinesterase (BChE) with an IC₅₀ of 7 μM. By inhibiting AChE, it prevents the hydrolysis of acetylcholine, prolonging its activity at nicotinic receptors at the neuromuscular junction.
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| ln Vitro |
Acetylcholinesterase (AChE) is rapidly and reversibly inhibited by ammonium chloride, which also has a substantial inhibitory impact on hAChE, with an inhibition constant Ki of 0.12 nM [1]. BChE is inhibited by ammonium chloride, with an IC50 value of 7 μM (hBChE)[2].
In vitro, Ambenonium chloride is a potent inhibitor of acetylcholinesterase. It inhibits human AChE with a Ki of 0.12 nM and an IC₅₀ of 0.7 nM. It also shows inhibitory effects towards BChE with an IC₅₀ of 7 μM. Its inhibition of AChE is rapidly reversible and non-covalent. The compound's high affinity for AChE makes it a valuable tool for studying cholinergic signaling. These in vitro activities confirm its mechanism as a potent and selective AChE inhibitor. |
| ln Vivo |
Long-term treatment of ammonium chloride (6 mg/kg; oral; daily; 30-60 d) can adversely impact neuromuscular transmission and promote hypersensitivity to stimuli in a mouse model of myasthenia gravis [3]. Ammonium chloride (6 mg/kg; oral; daily; 14 days) lowers the amount of AChRs in motor endplates [3].
In vivo, Ambenonium chloride is used to enhance cholinergic transmission. By inhibiting AChE, it increases the concentration of acetylcholine at the neuromuscular junction, which can improve muscle strength in conditions like myasthenia gravis. Its effects are of longer duration compared to neostigmine. The compound is administered orally and has been studied in animal models to assess its effects on motor end-plate fine structure and acetylcholine receptors. Its in vivo effects are consistent with its mechanism as a cholinesterase inhibitor. |
| Enzyme Assay |
In vitro enzyme assays for Ambenonium chloride measure its inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The enzyme activity is measured using a colorimetric method, such as the Ellman's assay, where the hydrolysis of acetylthiocholine is monitored spectrophotometrically. The compound is incubated with the enzyme and substrate, and the IC₅₀ or Ki values are calculated from the inhibition curves. These assays are standard for characterizing cholinesterase inhibitors and are for research purposes only.
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| Cell Assay |
In vitro cell-based assays for Ambenonium chloride are less common, as its primary mechanism is enzyme inhibition. However, its effects can be studied in neuronal or muscle cell cultures by measuring the compound's impact on cholinergic signaling. For example, the compound's ability to potentiate acetylcholine-induced responses can be assessed using electrophysiological techniques or by measuring intracellular calcium levels. Cytotoxicity assays (MTT or LDH release) can be performed to evaluate any potential toxic effects on cells. Standard cell culture conditions are used.
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| Animal Protocol |
Animal/Disease Models: Female Sprague Dawley rats with myasthenia gravis (weight 250 grams) [3]
Doses: 6 mg/kg Route of Administration: po (oral gavage); daily; 14, 30, 60, 90, 360 days ( Stop dosing 24 hrs (hrs (hours)) in advance) Experimental Results: Days 30-60 resulted in diminished general activity and hypersensitivity to stimuli in rats, but these behaviors disappeared on day 90. On day 360 of induced degeneration and simplification, postsynaptic folds, synaptic cleft widening, increased number of postsynaptic vesicles, and diminished number of AChRs in the postsynaptic membrane were observed. In vivo animal studies for Ambenonium chloride have been conducted to evaluate its long-term effects. For instance, rats have been administered the compound to study its effects on motor end-plate fine structure and acetylcholine receptors. Such studies involve chronic administration and subsequent histological and biochemical analysis of muscle tissue. Animal models of myasthenia gravis could also be used to assess its therapeutic efficacy. All procedures must comply with institutional animal care guidelines. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Ambenonium chloride are not fully detailed in the provided literature. It is a quaternary ammonium compound, which typically has poor oral bioavailability, but it is known to be orally active. Its half-life and metabolic profile would need to be determined from preclinical studies. The compound is intended for research and analytical applications. For research use, it should be stored under the conditions recommended in the Certificate of Analysis.
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| Toxicity/Toxicokinetics |
The toxicity profile of Ambenonium chloride is consistent with that of other cholinesterase inhibitors. Overstimulation of cholinergic receptors can lead to adverse effects such as muscle cramps, excessive salivation, and bradycardia. The compound is classified for research use only and not for human consumption. Standard safety precautions for handling potent enzyme inhibitors should be followed.
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| References |
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| Additional Infomation |
Ambenonium chloride is a symmetrical oxalamide bisquaternary ammonium salt with an ethyl and a 2-chlorobenzyl group attached to its nitrogen atom. It is an EC 3.1.1.8 (cholinesterase) inhibitor and a neurotransmitter. It is a quaternary ammonium salt and an organochloride. Ambenonium chloride is the chloride form of Ambenonium, a quaternary ammonium compound with parasympathomimetic activity. Ambenonium chloride is a rapidly acting, indirect cholinergic agonist that reversibly blocks acetylcholinesterase activity, thereby preventing the hydrolysis of acetylcholine and prolonging its action on nicotine receptors at the neuromuscular junction. It is a quaternary ammonium compound that inhibits cholinesterase activity, with an action similar to neostigmine but a longer duration of action. Ambenonium chloride is used to treat myasthenia gravis and must be taken orally. (Excerpt from Martindale Pharmacopoeia, 30th edition, page 1112)
Additional information: Ambenonium chloride has the CAS number 115-79-7. Its molecular formula is C₂₈H₄₂Cl₄N₄O₂ and its molecular weight is 608.47 g/mol. It is also known as WIN 8077. It is a rapidly reversible, non-covalent inhibitor of AChE with one of the highest known affinities. Ambenonium chloride is a research tool for studying cholinergic signaling and neuromuscular transmission. This product is for research use only and is not approved for clinical or therapeutic applications. |
| Molecular Formula |
C28H42CL4N4O2
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| Molecular Weight |
608.47
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| Exact Mass |
606.206
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| CAS # |
115-79-7
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| PubChem CID |
8288
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| Appearance |
White to off-white solid powder
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| Melting Point |
196-199°
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
38
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| Complexity |
614
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[Cl-].[Cl-].O=C(C(NCC[N+](CC1=CC=CC=C1Cl)(CC)CC)=O)NCC[N+](CC1=CC=CC=C1Cl)(CC)CC
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| InChi Key |
DXUUXWKFVDVHIK-UHFFFAOYSA-N
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| InChi Code |
1S/C28H40Cl2N4O2.2ClH/c1-5-33(6-2,21-23-13-9-11-15-25(23)29)19-17-31-27(35)28(36)32-18-20-34(7-3,8-4)22-24-14-10-12-16-26(24)30/h9-16H,5-8,17-22H2,1-4H32*1H
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| Chemical Name |
Ammonium, (oxalylbis(iminoethylene))bis((o-chlorobenzyl)diethyl-, dichloride
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| Synonyms |
Ambenonium dichloride, Ambenonium chloride,AI3-22370, Ambestigmin chloride, AI-322370,Oxamizil
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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 |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6435 mL | 8.2173 mL | 16.4347 mL | |
| 5 mM | 0.3287 mL | 1.6435 mL | 3.2869 mL | |
| 10 mM | 0.1643 mL | 0.8217 mL | 1.6435 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.
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