Acotiamide hydrochloride trihydrate | YM-443 | Z-338 | CAS#773092-05-0 | 185106-16-5 | 185104-11-4

MedKoo Cat#: 314263 | Name: Acotiamide hydrochloride trihydrate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Acotiamide, also known as YM-443 and Z-338, is a drug approved in Japan for the treatment of postprandial fullness, upper abdominal bloating, and early satiation due to functional dyspepsia. It acts as an acetylcholinesterase inhibitor. Note: The Approved drug API is a cotiamide HCl trihydrate (1:1:3)

Chemical Structure

Acotiamide hydrochloride trihydrate

CAS#773092-05-0 (HCl hydrate)

Theoretical Analysis

MedKoo Cat#: 314263

Name: Acotiamide hydrochloride trihydrate

CAS#: 773092-05-0 (HCl hydrate)

Chemical Formula: C21H37ClN4O8S

Exact Mass: 0.0000

Molecular Weight: 541.06

Elemental Analysis: C, 46.62; H, 6.89; Cl, 6.55; N, 10.36; O, 23.66; S, 5.93

Price and Availability

Size	Price	Availability
25mg	USD 90.00	Ready to ship
50mg	USD 150.00	Ready to ship
100mg	USD 225.00	Ready to ship
200mg	USD 350.00	Ready to ship
500mg	USD 650.00	Ready to ship
1g	USD 950.00	Ready to ship
2g	USD 1,450.00	Ready to ship
5g	USD 2,950.00	Ready to ship

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Related CAS #

773092-05-0 (HCl hydrate) 185104-11-4 (HCl) 185106-16-5 (free base)

Synonym

YM443; YM-443; YM 443; Z338; Z-338; Z 338; Acotiamide; Acotiamide hydrochloride trihydrate; Brand name: Acofide.

IUPAC/Chemical Name

N-(2-(diisopropylamino)ethyl)-2-(2-hydroxy-4,5-dimethoxybenzamido)thiazole-4-carboxamide hydrochloride trihydrate.

InChi Key

NPTDXIXCQCFGKC-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H30N4O5S.ClH.3H2O/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;3*1H2

SMILES Code

O=C(C1=CSC(NC(C2=CC(OC)=C(OC)C=C2O)=O)=N1)NCCN(C(C)C)C(C)C.[H]Cl.[H]O[H].[H]O[H].[H]O[H]

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO.

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# CAS#773092-05-0 (Acotiamide HCl hydrate, 1:1:3); CAS#185104-11-4(Acotiamide HCl, 1:1); CAS#185106-16-5 (Acotiamide free base)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC60412

QC Data

View QC data: current batch, Lot#TZC60412

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Acotiamide monohydrochloride trihydrate enhances acetylcholine released by enteric neurons through muscarinic receptor antagonism and acetylcholinesterase (AChE) inhibition.

In vitro activity:

TNF-α production in 1 μg/mL LPS-stimulated NR8383 cells treated with MCP-1 (100 pg/mL) was significantly elevated compared to that in LPS (1 μg/mL)-stimulated NR8383 cells (Figure 7A) (P < .01). Interestingly, acotiamide treatment (10, 30, and 100 μmol/L) significantly reduced TNF-α productions in LPS (1 μg/mL)-stimulated NR8383 cells treated with MCP-1 (100 pg/mL) (Figure 7A) (P < .05, respectively). IL-6 production in LPS (1 μg/mL)-stimulated NR8383 cells treated with MCP-1 (100 pg/ml) was significantly elevated compared to that in LPS (1 μg/mL)-stimulated NR8383 cells (Figure 7B) (P < .05). Interestingly, 30 μmol/L treatment with acotiamide significantly reduced IL-6 production in 1 μg/mL LPS-stimulated NR8383 cells treated with MCP-1 (100 pg/mL) (Figure 7B) (P < .05), and then, IL-4 productions were not increased in LPS alone or LPS-stimulated NR8383 cells treated with MCP-1 (Figure 7C). Reference: Neurogastroenterol Motil. 2020 Aug;32(8):e13813. https://pubmed.ncbi.nlm.nih.gov/32030855/

In vivo activity:

As shown in Fig. 3A, Z-338 (10 µM) markedly enhanced the frequency of spontaneous unit discharges in AP rat neurons with relatively low (<1~2 unit discharges/sec) firing rates. The acceleratory effect of Z-338 was reversible, although the effects lasted for prolonged period (more than 1 hour) after wash out of Z-338. In neurons with relatively higher firing rates (>3~5 unit discharges/sec), on the other hand, Z-338 showed little effect on the firing rates (Fig. 3B). Reference: J Smooth Muscle Res. 2010;46(1):31-47. https://www.jstage.jst.go.jp/article/jsmr/46/1/46_1_31/_pdf/-char/en

	Solvent	mg/mL	mM
Solubility
	DMSO	112.5	207.93
	Ethanol	20.0	36.96
	Water	5.0	9.24

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 541.06 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Yamawaki H, Futagami S, Sakasegawa N, Murakami M, Agawa S, Ikeda G, Noda H, Kirita K, Gudis K, Higuchi K, Kodaka Y, Ueki N, Iwakiri K. 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. doi: 10.1111/nmo.13813. Epub 2020 Feb 7. PMID: 32030855. 2. Hashimoto K, Tashima K, Imai T, Matsumoto K, Horie S. The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia. J Pharmacol Sci. 2021 Jan;145(1):122-129. doi: 10.1016/j.jphs.2020.10.006. Epub 2020 Nov 11. PMID: 33357770. 3. Akaike H, Jang II, Hori N, Ogawa S, Ito Y, Akaike N. Effects of Z-338, a novel gastroprokinetic agent, on the actions of excitatory and inhibitory neurotransmitters on neurons in area postrema. J Smooth Muscle Res. 2010;46(1):31-47. doi: 10.1540/jsmr.46.31. PMID: 20383032.

In vitro protocol:

In vivo protocol:

1. Hashimoto K, Tashima K, Imai T, Matsumoto K, Horie S. The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia. J Pharmacol Sci. 2021 Jan;145(1):122-129. doi: 10.1016/j.jphs.2020.10.006. Epub 2020 Nov 11. PMID: 33357770. 2. Akaike H, Jang II, Hori N, Ogawa S, Ito Y, Akaike N. Effects of Z-338, a novel gastroprokinetic agent, on the actions of excitatory and inhibitory neurotransmitters on neurons in area postrema. J Smooth Muscle Res. 2010;46(1):31-47. doi: 10.1540/jsmr.46.31. PMID: 20383032.

1: Mayanagi S, Kishino M, Kitagawa Y, Sunamura M. Efficacy of acotiamide in combination with esomeprazole for functional dyspepsia refractory to proton-pump inhibitor monotherapy. Tohoku J Exp Med. 2014;234(3):237-40. PubMed PMID: 25382232. 2: Zai H, Matsueda K, Kusano M, Urita Y, Saito Y, Kato H. Effect of acotiamide on gastric emptying in healthy adult humans. Eur J Clin Invest. 2014 Dec;44(12):1215-21. doi: 10.1111/eci.12367. PubMed PMID: 25370953. 3: Xiao G, Xie X, Fan J, Deng J, Tan S, Zhu Y, Guo Q, Wan C. Efficacy and safety of acotiamide for the treatment of functional dyspepsia: systematic review and meta-analysis. ScientificWorldJournal. 2014;2014:541950. doi: 10.1155/2014/541950. Epub 2014 Aug 12. PubMed PMID: 25197703; PubMed Central PMCID: PMC4146483. 4: Sun Y, Song G, McCallum RW. Evaluation of acotiamide for the treatment of functional dyspepsia. Expert Opin Drug Metab Toxicol. 2014 Aug;10(8):1161-8. doi: 10.1517/17425255.2014.920320. Epub 2014 May 31. PubMed PMID: 24881488. 5: Matsunaga Y, Tanaka T, Saito Y, Kato H, Takei M. [Pharmacological and clinical profile of acotiamide hydrochloride hydrate (Acofide(Â®) Tablets 100 mg), a novel therapeutic agent for functional dyspepsia (FD)]. Nihon Yakurigaku Zasshi. 2014 Feb;143(2):84-94. Review. Japanese. PubMed PMID: 24531902. 6: Nowlan ML, Scott LJ. Acotiamide: first global approval. Drugs. 2013 Aug;73(12):1377-83. doi: 10.1007/s40265-013-0100-9. Erratum in: Drugs. 2014 Jun;74(9):1059. Nolan, Mary L [corrected to Nowlan, Mary L]. PubMed PMID: 23881665. 7: Altan E, Masaoka T, FarrÃ© R, Tack J. Acotiamide, a novel gastroprokinetic for the treatment of patients with functional dyspepsia: postprandial distress syndrome. Expert Rev Gastroenterol Hepatol. 2012 Sep;6(5):533-44. doi: 10.1586/egh.12.34. Review. PubMed PMID: 23061703. 8: Nagahama K, Matsunaga Y, Kawachi M, Ito K, Tanaka T, Hori Y, Oka H, Takei M. Acotiamide, a new orally active acetylcholinesterase inhibitor, stimulates gastrointestinal motor activity in conscious dogs. Neurogastroenterol Motil. 2012 Jun;24(6):566-74, e256. doi: 10.1111/j.1365-2982.2012.01912.x. Epub 2012 Mar 19. PubMed PMID: 22429221. 9: Kusunoki H, Haruma K, Manabe N, Imamura H, Kamada T, Shiotani A, Hata J, Sugioka H, Saito Y, Kato H, Tack J. Therapeutic efficacy of acotiamide in patients with functional dyspepsia based on enhanced postprandial gastric accommodation and emptying: randomized controlled study evaluation by real-time ultrasonography. Neurogastroenterol Motil. 2012 Jun;24(6):540-5, e250-1. doi: 10.1111/j.1365-2982.2012.01897.x. Epub 2012 Mar 4. PubMed PMID: 22385472. 10: McLarnon A. Dyspepsia: Acotiamide can relieve symptoms of functional dyspepsia. Nat Rev Gastroenterol Hepatol. 2012 Jan 17;9(2):62. doi: 10.1038/nrgastro.2011.262. PubMed PMID: 22249733.