Acotiamide

Names

[ Name ]:
Acotiamide

[Synonym ]:
Acotiamide
MZ-338
N-[2-(Diisopropylamino)ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1,3-thiazole-4-carboxamide
UNII-D42OWK5383
4-Thiazolecarboxamide, N-[2-[bis(1-methylethyl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-

Biological Activity

[Description]:

Acotiamide is an orally active, selective and reversible acetylcholinesterase (AChE) inhibitor, with IC50 of 1.79 μM. Acotiamide can enhance gastric contractility and accelerate delayed gastric emptying. Acotiamide has the potential for the research of functional dyspepsia involving gastric motility dysfunction and intestinal inflammatory[1][2][3].

[Related Catalog]:

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

Signaling Pathways >> Neuronal Signaling >> AChE

[Target]

IC50: 1.79 μM (AChE)

[In Vitro]

Acotiamide (10, 30, 100 μM; 1 hour) reduces expression levels of IκB-α phosphorylation in LPS- and MCP-1-stimulated macrophage cell lines[1]. Cell Viability Assay[1] Cell Line: NR8383, macrophage Concentration: 10, 30, 100 μM Incubation Time: 1 hour Result: Significantly reduced both TNF-α and IL-6 productions in LPS/MCP-1-stimulated NR8383 cells.

[In Vivo]

Acotiamide (0.3, 1, 3 mg/kg; i.v./3, 10, 30 mg/kg; p.o.) increases the postprandial gastric motility index in a dose-dependent manner[2]. Acotiamide (0.83 mg/kg; i.v.; once) inhibits AChE in rat stomach with IC50 of 1.79 μM[3]. Animal Model: Male mongrel dogs (9-11 kg), Male beagle dogs (9.6-12.9 kg)[2] Dosage: 0.3, 1, 3, 10, 30 mg/kg Administration: Intravenous injection; once Result: Increased the postprandial gastric motility. Animal Model: Male Sprague-Dawley rats (aged 6-7 weeks)[3] Dosage: 0.83 mg/kg Administration: Intravenous injection; once. Result: Effectively improved functional dyspepsia by inhibiting AChE in rat stomach.

[References]

[1]. Kazuyoshi Y oshii, et al. Physiologically-Based Pharmacokinetic and Pharmacodynamic Modeling for the Inhibition of Acetylcholinesterase by Acotiamide, A Novel Gastroprokinetic Agent for the Treatment of Functional Dyspepsia, in Rat Stomach. Pharmaceutical Research, 33(2), 292–300.

[2]. Hiroshi Yamawaki, et al. Acotiamide attenuates central urocortin 2-induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF-α productions in LPS-stimulated macrophage cell lines. Neurogastroenterol Motil. 2020 Aug;32(8):e13813.

[3]. Matsunaga Y, Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011 Mar;336(3):791-800.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Molecular Formula ]:
C₂₁H₃₀N₄O₅S

[ Molecular Weight ]:
450.552

[ Exact Mass ]:
450.193695

[ PSA ]:
148.24000

[ LogP ]:
3.56

[ Index of Refraction ]:
1.592

[ Storage condition ]:
-20℃

Related Compounds

The content on this webpage is sourced from various professional data sources. If you have any questions or concerns regarding the content, please feel free to contact service1@chemsrc.com.