Zamifenacin (C007B-433636)

Zamifenacin (UK-76654) is a potent gut-selective muscarinic M3 receptor antagonist. Zamifenacin significantly reduces colonic motility in irritable bowel syndromeIn VivoZamifenacin exhibits moderate oral bioavailability (mouse 26%, rat 64%, dog 100%) and C max (mouse 92, rat 905, dog 416 ng/mL) following oral administration (mouse 13.2, rat 20 and, dog 5 mg/kg). Zamifenacin exhibits terminal elimination half-lives (mouse 2.1, rat 6.0 and, dog 1.1 h) due to high plasma clearance (68, 35, and 39 mL/min/kg respectively) combined with large volumes of distribution (12.5, 19.0, and 3.5 L/kg respectively) following intravenous administration (mouse 5.3, rat 5.0 and, dog 1.0 mg/kg). MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male CDl mice (mean weight 23 g)Dosage: 5.3 mg/kg for i.v.; 13.2 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous administration and oral administration Result: Oral bioavailability (26%), C max (92 ng/mL), T 1/2 (2.1 h). Animal Model: Male and female CD rats (mean weight 210 g)Dosage: 5.0 mg/kg for i.v.; 20 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous administration and oral administration Result: Oral bioavailability (64%), C max (905 ng/mL), T 1/2 (6.0 h). Animal Model: Male and two female beagle dogs (13-16 kg)Dosage: 1.0 mg/kg for i.v.; 5 mg/kg for oral (Pharmacokinetic Analysis) Administration: Intravenous administration and oral administration Result: Oral bioavailability (100%), C max (416 ng/mL), T 1/2 (1.1 h).Form:SolidIC50& Target:Muscarinic M3 receptor. Specification: 0.99 Molecular Formula: C27H29NO3 Molecular Weight: 415.52 PubChem CID: 3086618 Isomeric SMILES: C1C[C@H](CN(C1)CCC2=CC3=C(C=C2)OCO3)OC(C4=CC=CC=C4)C5=CC=CC=C5