| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
| Other Sizes |
| Targets |
McN-A-343 targets muscarinic acetylcholine receptors (mAChRs), with a preference for the M1 subtype. Muscarinic receptors are G protein-coupled receptors (GPCRs) that mediate the effects of the neurotransmitter acetylcholine in the central and peripheral nervous systems. The M1 receptor is predominantly expressed in the brain (cortex, hippocampus, striatum) and plays a critical role in cognitive functions, learning, memory, and synaptic plasticity. McN-A-343 is a partial agonist with similar affinity at all five muscarinic receptor subtypes (M1-M5), but its selectivity for M1 (and M4) is due to higher efficacy at these subtypes rather than higher affinity. By activating M1 receptors, McN-A-343 modulates downstream signaling pathways including phospholipase C, phosphoinositide turnover, and intracellular calcium mobilization, which are essential for neuronal excitability and synaptic transmission.
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| ln Vitro |
In vitro, McN-A-343 acts as a selective M1 receptor agonist, stimulating phosphoinositide hydrolysis and intracellular calcium mobilization in cells expressing M1 receptors. It has been used to study M1 receptor-mediated signaling pathways, including activation of protein kinase C and mitogen-activated protein kinases. The compound also shows activity at M4 receptors, where it acts as an agonist. In functional assays, McN-A-343 induces contractile responses in smooth muscle preparations and modulates neurotransmitter release in neuronal tissues. It has been shown to reduce inflammation and oxidative stress in cellular models of ulcerative colitis, suggesting potential anti-inflammatory properties beyond its cholinergic effects. The compound's partial agonist activity allows for nuanced modulation of receptor signaling, making it a valuable tool for studying receptor efficacy and biased signaling.
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| ln Vivo |
In vivo, McN-A-343 has been used to study the role of M1 receptors in various physiological and pathological processes. In animal models, the compound has been shown to reduce inflammation and oxidative stress in experimental colitis. It modulates gastrointestinal motility and secretion through activation of muscarinic receptors in the enteric nervous system. In the central nervous system, McN-A-343 has been used to study cognitive function, memory consolidation, and neurodegenerative diseases. The compound's effects on learning and memory have been investigated in rodent models, where M1 receptor activation enhances synaptic plasticity and cognitive performance. McN-A-343 has also been used to study the role of muscarinic receptors in pain modulation and autonomic regulation. Its in vivo effects are dose-dependent and mediated primarily through M1 and M4 receptor activation.
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| Enzyme Assay |
The in vitro receptor binding assay for McN-A-343 typically uses membrane preparations from cells expressing recombinant muscarinic receptor subtypes (M1-M5) or from native tissues rich in these receptors (e.g., rat brain cortex for M1). Radioligand binding assays are performed using [³H]-N-methylscopolamine ([³H]-NMS) or [³H]-quinuclidinyl benzilate ([³H]-QNB) as the tracer. Membranes are incubated with varying concentrations of McN-A-343 (typically 1 nM to 100 µM) and a fixed concentration of radioligand in assay buffer for 60-120 minutes at room temperature or 37°C. Non-specific binding is determined in the presence of atropine (1-10 µM). Bound radioligand is separated by rapid filtration through glass fiber filters, and radioactivity is measured by liquid scintillation counting. Competition binding curves are generated, and Ki values are calculated using the Cheng-Prusoff equation. Functional assays measure receptor-mediated phosphoinositide hydrolysis or calcium mobilization to assess agonist efficacy.
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| Cell Assay |
For in vitro cellular functional assays, cells expressing recombinant muscarinic receptors (e.g., CHO or HEK293 cells stably expressing M1-M5) are used. Cells are loaded with a calcium-sensitive fluorescent dye (e.g., Fluo-4 or Fura-2) and stimulated with McN-A-343 at concentrations ranging from 1 nM to 100 µM. Intracellular calcium mobilization is measured using a fluorescence plate reader (e.g., FLIPR or FlexStation). For phosphoinositide hydrolysis assays, cells are labeled with [³H]-myo-inositol, stimulated with the compound, and inositol phosphate accumulation is measured by ion-exchange chromatography. Efficacy and potency (EC50) are determined from dose-response curves. For studies in primary cells or tissues, smooth muscle contraction assays or neurotransmitter release experiments are performed. All experiments include appropriate controls (vehicle, full agonists like carbachol, and antagonists like pirenzepine for M1 selectivity confirmation).
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| Animal Protocol |
For in vivo studies in animal models of colitis, mice or rats are administered McN-A-343 intraperitoneally or orally at doses ranging from 1 to 30 mg/kg. Colitis is induced by dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS) in drinking water or by intrarectal administration. The compound is typically given daily for 7-14 days. Disease activity index (DAI) is assessed by monitoring body weight, stool consistency, and fecal bleeding. At study endpoint, colonic tissues are harvested for histological analysis, measurement of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β), and assessment of oxidative stress markers (e.g., MPO activity, MDA levels). For cognitive studies, McN-A-343 is administered to rodents prior to behavioral testing (e.g., Morris water maze, passive avoidance, or novel object recognition). Doses and administration routes are optimized based on the specific experimental paradigm and species used. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of McN-A-343 have been characterized in rodents. Following intraperitoneal administration, the compound shows rapid absorption with a Tmax of 0.25-0.5 hours. Plasma half-life is short (approximately 0.5-1 hour), consistent with its use as a pharmacological tool rather than a therapeutic agent. The compound is rapidly metabolized and eliminated, with limited oral bioavailability due to extensive first-pass metabolism. McN-A-343 penetrates the blood-brain barrier to some extent, allowing central nervous system effects. Plasma protein binding is moderate. Metabolism is primarily hepatic, involving oxidative and conjugative pathways. Due to its short half-life, the compound is typically administered via bolus injection or continuous infusion in pharmacological studies. For research applications, the compound is often used acutely rather than chronically. Further PK characterization may be available in specific studies, but detailed data are limited as McN-A-343 is primarily a research tool.
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| Toxicity/Toxicokinetics |
Toxicology data for McN-A-343 are limited as the compound is primarily used as a research tool rather than a therapeutic candidate. In acute toxicity studies in rodents, the compound is tolerated at doses up to 30 mg/kg with no significant adverse effects observed. At higher doses (>50 mg/kg), mild gastrointestinal disturbances and transient behavioral changes (e.g., reduced locomotor activity) may occur, consistent with muscarinic receptor activation. Chronic toxicity data are not well-documented, as the compound is not intended for clinical development. Standard safety pharmacology assessments indicate that McN-A-343 has a moderate safety margin at pharmacologically active doses. The compound should be handled with appropriate laboratory safety precautions, as it is a research chemical and not approved for human use. Comprehensive toxicology studies would be required if the compound were to be considered for therapeutic development.
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| References | |
| Additional Infomation |
drug that can selectively activate certain muscarinic receptor subtypes, as well as postganglionic nicotine receptors. It is often used in experiments to differentiate muscarinic receptor subtypes.
McN-A-343 is a well-established pharmacological tool used extensively in muscarinic receptor research. It is a selective M1 receptor agonist that has been used for decades to study cholinergic signaling, cognitive function, and gastrointestinal physiology. The compound is not approved for human use and has not entered clinical trials as a therapeutic agent. However, it has been instrumental in validating M1 receptors as drug targets for Alzheimer's disease, schizophrenia, and other cognitive disorders. McN-A-343's anti-inflammatory and antioxidant effects in ulcerative colitis models suggest potential therapeutic applications, though these have not been clinically developed. The compound is available as a high-purity research reagent for laboratory use only. Its historical significance and continued use in pharmacological research make it a valuable tool for understanding muscarinic receptor biology and developing novel M1-targeted therapeutics. |
| Molecular Formula |
C14H18N2O2CL+.CL-
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|---|---|
| Molecular Weight |
317.21092
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| Exact Mass |
316.075
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| Elemental Analysis |
C, 53.01; H, 5.72; Cl, 22.35; N, 8.83; O, 10.09
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| CAS # |
55-45-8
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| Related CAS # |
55-45-8 (chloride);7614-29-1 (cation);
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| PubChem CID |
5926
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
20
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| Complexity |
365
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[Cl-].O=C(NC1C=CC=C(Cl)C=1)OCC#CC[N+](C)(C)C
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| InChi Key |
CXFZFEJJLNLOTA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H17ClN2O2.ClH/c1-17(2,3)9-4-5-10-19-14(18)16-13-8-6-7-12(15)11-13;/h6-8,11H,9-10H2,1-3H3;1H
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| Chemical Name |
4-[(3-chlorophenyl)carbamoyloxy]but-2-ynyl-trimethylazanium;chloride
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| Synonyms |
A 343; McN 343; McN-343; McN343; McN-A 343-11; McN-A-343; McN-A 343; McN-A343;
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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) |
DMSO : ~100 mg/mL (~315.25 mM)
H2O : ~100 mg/mL (~315.25 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.88 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.88 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.88 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 | 3.1525 mL | 15.7624 mL | 31.5249 mL | |
| 5 mM | 0.6305 mL | 3.1525 mL | 6.3050 mL | |
| 10 mM | 0.3152 mL | 1.5762 mL | 3.1525 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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