Bulk supply Acotiamide hydrochloride trihydrate CAS No.773092-05-0 CAS NO.773092-05-0

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In June 2013, the Ministry of Health, Labor and Welfare in Japan approved acotiamide (also referred to as Z-338 and YM443), for the treatment of postprandial fullness, upper abdominal bloating, and early satiation due to functional dyspepsia (FD). Acotiamide enhances acetylcholine release from enteric neurons through selective muscarinic acetylcholine receptor M1, M2 antagonism, and inhibition of AChE, thereby enhancing gastric emptying and gastric accommodation. Acotiamide inhibits the acetylcholine-induced Ca²⁺-activated Cl^-current with an IC₅₀ of 1.8 μM in oocytes expressing muscarinic M1 receptors and in oocytes expressing muscarinic M2 receptors, acotiamide inhibited the acetylcholine-induced K⁺ currents with an IC₅₀ of 10.1 μM. However, studies in conscious dogs, guinea-pig gastric muscle strips and assays with human cholinesterase indicate that acotiamide inhibits AChE with a Ki of 610 nM suggesting that acotiamide stimulates gastric motility mainly by inhibiting AChE activation. In a restraint stress-induced rat model, acotiamide significantly improved delayed gastric emptying and feeding inhibition but did not affect normal gastric emptying or feeding in intact rats. A synthetic route to acotiamide that employs pyridine hydrochloride to selectively cleave a 2-substituted methyl ether from a 2,4,5-trimethoxy benzamide intermediate, as a key step, has been reported.