| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Zamifenacin targets the muscarinic M3 receptor, a G protein-coupled receptor involved in smooth muscle contraction and glandular secretion. It acts as a selective M3 receptor antagonist. Zamifenacin shows selectivity for M3 over M2 receptors, which is important for reducing cardiac side effects such as bradycardia. The compound also exhibits activity at other muscarinic receptor subtypes with lower affinity.
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| ln Vitro |
In vitro, Zamifenacin acts as a potent and selective antagonist at the muscarinic M3 receptor. It inhibits M3 receptor-mediated smooth muscle contraction in isolated tissue preparations. The compound demonstrates selectivity for M3 over M2 receptors, with a favorable selectivity ratio. Specific IC50 or Ki values for receptor binding are available from pharmacological studies.
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| ln Vivo |
After oral dosing (13.2 for mice, 20 for rats, and 5 mg/kg for dogs), zamifenacin has moderate oral bioavailability (26% in mice, 64% in rats, and 100% in dogs) and Cmax (92 in mice, 905 in rats, and 416 ng/mL in dogs) [2]. Large distribution volume (12.5, 19.0, and 3.5 L/kg after intravenous injection; 5.3 in mice, 5.0 in rats, and 1.0 mg/dog in dogs, respectively) and high plasma clearance (68, 35, and 39 mL/min/kg, respectively) are the reasons for this [2].
In vivo, Zamifenacin has been investigated for the treatment of irritable bowel syndrome (IBS) and other gastrointestinal disorders. As an M3 receptor antagonist, it reduces gastrointestinal smooth muscle contraction and spasm, thereby alleviating symptoms of IBS. The compound's M3 selectivity reduces the risk of cardiac side effects compared to non-selective muscarinic antagonists. |
| Enzyme Assay |
The in vitro receptor binding assay for Zamifenacin involves measuring its affinity for muscarinic M3 and M2 receptors. Radiolabeled ligand binding assays are performed using membrane preparations from cells expressing M3 or M2 receptors. Varying concentrations of Zamifenacin are incubated with the receptor preparation, and binding affinity (IC50 or Ki) is determined. The compound's selectivity for M3 over M2 is calculated from the ratio of binding affinities.
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| Cell Assay |
In vitro cellular assays for Zamifenacin involve treating cultured smooth muscle cells or tissues expressing muscarinic M3 receptors with varying concentrations of the compound. M3 receptor-mediated calcium mobilization or contraction is measured. The compound's ability to block M3-mediated responses is assessed. Selectivity over M2 receptors is confirmed by comparing effects on M2-mediated responses in cardiac cells.
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| Animal Protocol |
Animal/Disease Models: Male CD1 mice (average weight 23g) [2]
Doses: 5.3 mg/kg, intravenous (iv) (iv)injection; oral 13.2 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)administration and oral administration Experimental Results: oral bioavailability (26%), Cmax (92 ng/mL), T1/2 (2.1 h). Animal/Disease Models: Male and female CD rats (average body weight 210 g) [2] Doses: 5.0 mg/kg, intravenous (iv) (iv)injection; oral 20 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: intravenous (iv) (iv)administration and oral administration Experimental Results: Oral bioavailability (64%), Cmax (905 ng/mL) , T1/2 (6.0 h). Animal/Disease Models: Male and two female beagle dogs (13-16 kg) [2] Doses: 1.0 mg/kg intravenously (iv) (iv)(iv); 5 mg/kg orally (pharmacokinetic/PK/PK analysis) Mode of Route of Administration: intravenous (iv) (iv)and oral administration Experimental Results: Oral bioavailability (100%), Cmax (416 ng/mL), T1/2 (1.1 h). In vivo animal experiments for Zamifenacin typically use rodent models of gastrointestinal motility or IBS. The compound is administered orally or intraperitoneally at various doses. Gastrointestinal transit time, colonic motility, and visceral pain responses are measured. The compound's efficacy in reducing gastrointestinal spasm and pain is assessed. Cardiac effects such as heart rate changes are monitored to evaluate M2 selectivity. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of Zamifenacin have been characterized in preclinical studies. As a small molecule M3 receptor antagonist, it is expected to have oral bioavailability and reasonable tissue distribution. The compound has a molecular weight of 426.55 (C27H30N2O3). Specific PK parameters including half-life, Cmax, and metabolic pathways are available from preclinical studies.
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| Toxicity/Toxicokinetics |
Zamifenacin has been evaluated in clinical trials for irritable bowel syndrome. As an M3 receptor antagonist, potential adverse effects may include dry mouth, constipation, blurred vision, and urinary retention, which are class effects of muscarinic antagonists. The compound's M3 selectivity may reduce cardiac side effects. Complete toxicology data are available from the compound's clinical development program.
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| References |
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| Additional Infomation |
(3R)-1-[2-(1,3-benzodioxacyclopenten-5-yl)ethyl]-3-(diphenylmethyl)oxoperidine is a diarylmethane.
Zamifenacin (CAS#: 127308-82-1) is a potent and selective muscarinic M3 receptor antagonist investigated for the treatment of irritable bowel syndrome (IBS). It exhibits selectivity for M3 over M2 receptors, reducing the risk of cardiac side effects. Zamifenacin inhibits M3 receptor-mediated smooth muscle contraction in the gastrointestinal tract. The compound is not approved for clinical use and remains an investigational agent. |
| Molecular Formula |
C27H29NO3
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|---|---|
| Molecular Weight |
415.533
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| Exact Mass |
415.215
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| CAS # |
127308-82-1
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| Related CAS # |
Zamifenacin fumarate;127308-98-9
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| PubChem CID |
3086618
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.2g/cm3
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| Boiling Point |
532.5ºC at 760mmHg
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| Flash Point |
145.6ºC
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| LogP |
5.166
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
513
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1C[C@H](CN(C1)CCC2=CC3=C(C=C2)OCO3)OC(C4=CC=CC=C4)C5=CC=CC=C5
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| InChi Key |
BDNFQGRSKSQXRI-XMMPIXPASA-N
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| InChi Code |
InChI=1S/C27H29NO3/c1-3-8-22(9-4-1)27(23-10-5-2-6-11-23)31-24-12-7-16-28(19-24)17-15-21-13-14-25-26(18-21)30-20-29-25/h1-6,8-11,13-14,18,24,27H,7,12,15-17,19-20H2/t24-/m1/s1
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| Chemical Name |
(3R)-3-benzhydryloxy-1-[2-(1,3-benzodioxol-5-yl)ethyl]piperidine
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| Synonyms |
UK-76654; UK76654; UK 76654
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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 (~240.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.02 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 (6.02 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.02 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 | 2.4066 mL | 12.0328 mL | 24.0657 mL | |
| 5 mM | 0.4813 mL | 2.4066 mL | 4.8131 mL | |
| 10 mM | 0.2407 mL | 1.2033 mL | 2.4066 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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