Acotiamide HCl is an orally bioactive, selective and reversible inhibitor of acetylcholine alkaline esterase (AChE) with IC50 of 1.79 μM. Acotiamide HCl increases gastric contractility and accelerates delayed gastric emptying. Acotiamide HCl may be utilized to study functional dyspepsia and intestinal inflammation caused by gastric motility disorders.

Physicochemical Properties

Molecular Formula	C21H31CLN4O5S
Molecular Weight	487.0126
Exact Mass	486.17
CAS #	185104-11-4
Related CAS #	Acotiamide monohydrochloride trihydrate;773092-05-0;Acotiamide;185106-16-5;Acotiamide-d6 hydrochloride;Acotiamide-d6
PubChem CID	9957090
Appearance	Typically exists as solid at room temperature
LogP	4.727
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	10
Heavy Atom Count	32
Complexity	586
Defined Atom Stereocenter Count	0
SMILES	Cl[H].S1C(N([H])C(C2C(=C([H])C(=C(C=2[H])OC([H])([H])[H])OC([H])([H])[H])O[H])=O)=NC(=C1[H])C(N([H])C([H])([H])C([H])([H])N(C([H])(C([H])([H])[H])C([H])([H])[H])C([H])(C([H])([H])[H])C([H])([H])[H])=O
InChi Key	VQEKQYLTAIVCBW-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H30N4O5S.ClH/c1-12(2)25(13(3)4)8-7-22-20(28)15-11-31-21(23-15)24-19(27)14-9-17(29-5)18(30-6)10-16(14)26;/h9-13,26H,7-8H2,1-6H3,(H,22,28)(H,23,24,27);1H
Chemical Name	N-[2-[di(propan-2-yl)amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl)amino]-1,3-thiazole-4-carboxamide;hydrochloride
HS Tariff Code	2934.99.9001
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)

Biological Activity

ln Vitro	In macrophage cell lines treated with LPS and MCP-1, Acotiamide Hydrochronide (10, 30, 100 μM; 1 hour) decreases the expression level of IκB-α phosphorylation [1].
ln Vivo	In a dose-dependent manner, acocamide hydrochloride (0.3, 1, 3 mg/kg; iv/3, 10, 30 mg/kg; po) raises the postprandial stomach motility index [2]. With an IC50 value of 1.79 μM, acocamide hydrochloride (0.83 mg/kg; intravenous injection; once) inhibits AChE in the stomach of rats [3].
Cell Assay	Cell viability assay [1] Cell Types: NR8383, macrophage Tested Concentrations: 10, 30, 100 μM Incubation Duration: 1 hour Experimental Results: The production of TNF-α and IL-6 in NR8383 cells stimulated by LPS/MCP-1 was significant reduce.
Animal Protocol	Animal/Disease Models: Male mongrel dog (9-11 kg), male beagle dog (9.6-12.9 kg) [2] Doses: 0.3, 1, 3, 10, 30 mg/kg Route of Administration: intravenous (iv) (iv)injection; once. Experimental Results: Gastric motility increased after meals. Animal/Disease Models: Male SD (SD (Sprague-Dawley)) rats (6-7 weeks old) [3]. Doses: 0.83 mg/kg Route of Administration: intravenous (iv) (iv)injection; once. Experimental Results: Functional dyspepsia was effectively improved by inhibiting AChE in the stomach of rats.
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 [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-
Additional Infomation	See also: Acotiamide Hydrochloride (annotation moved to).

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0533 mL	10.2667 mL	20.5335 mL
	5 mM	0.4107 mL	2.0533 mL	4.1067 mL
	10 mM	0.2053 mL	1.0267 mL	2.0533 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.