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Details

Stereochemistry ACHIRAL
Molecular Formula C21H30N4O5S
Molecular Weight 450.552
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ACOTIAMIDE

SMILES

COC1=CC(O)=C(C=C1OC)C(=O)NC2=NC(=CS2)C(=O)NCCN(C(C)C)C(C)C

InChI

InChIKey=TWHZNAUBXFZMCA-UHFFFAOYSA-N
InChI=1S/C21H30N4O5S/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)

HIDE SMILES / InChI

Molecular Formula C21H30N4O5S
Molecular Weight 450.552
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21123674 | https://www.ncbi.nlm.nih.gov/pubmed/10871292 | https://www.astellas.com/en/corporate/news/pdf/130605_1_Eg.pdf

Acotiamide (Acofide(®)), an oral first-in-class prokinetic drug, is under global development by Zeria Pharmaceutical Co. Ltd and Astellas Pharma Inc. for the treatment of patients with functional dyspepsia. The drug modulates upper gastrointestinal motility to alleviate abdominal symptoms resulting from hypomotility and delayed gastric emptying. It exerts its activity in the stomach via muscarinic receptor inhibition, resulting in enhanced acetylcholine release and inhibition of acetylcholinesterase activity. Acofide® is launched in Japan for treating functional dyspepsia.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ACOFIDE

Approved Use

Acofide (Acotiamide hydrochloride hydrate) improves gastrointestinal motility and promotes excretion of stomach contents by inhibiting acetylcholinesterase activities. It is usually used for the treatment of postprandial fullness, upper abdominal bloating, and early satiation due to functional dyspepsia.

Launch Date

2013
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
25.71 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
200 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
168.2 ng/mL
300 mg 3 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
451.59 ng/mL
900 mg 3 times / day multiple, oral
dose: 900 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
511.75 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
537.2 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1215 ng × h/mL
300 mg 3 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1659.57 ng × h/mL
900 mg 3 times / day multiple, oral
dose: 900 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.49 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
8.99 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.25 h
300 mg 3 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
14.92%
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
14.92%
300 mg 3 times / day multiple, oral
dose: 300 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
14.92%
900 mg 3 times / day multiple, oral
dose: 900 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ACOTIAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Other AEs: Constipation, Diarrhea...
Other AEs:
Constipation (2.2%)
Diarrhea (2.2%)
ALT increased (1.5%)
Gamma-glutamyltransferase increased (1%)
Sources:
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Disc. AE: Nausea, Dyspepsia...
AEs leading to
discontinuation/dose reduction:
Nausea (1.4%)
Dyspepsia (0.97%)
Constipation (0.48%)
Eructation (0.48%)
Gastrointestinal sounds abnormal (0.48%)
Reflux gastritis (0.48%)
Appetite decreased NOS (0.48%)
Dysgeusia (0.48%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Gamma-glutamyltransferase increased 1%
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
ALT increased 1.5%
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Constipation 2.2%
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Diarrhea 2.2%
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Appetite decreased NOS 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Constipation 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Dysgeusia 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Eructation 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Gastrointestinal sounds abnormal 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Reflux gastritis 0.48%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Dyspepsia 0.97%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Nausea 1.4%
Disc. AE
100 mg 3 times / day multiple, oral
Recommended
Dose: 100 mg, 3 times / day
Route: oral
Route: multiple
Dose: 100 mg, 3 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major [Km 1430 uM]
major [Km 43.13 uM]
major
minor
minor
no
no
no
no
weak [Km 697 uM]
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
weak
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Prokinetics and fundic relaxants in upper functional GI disorders.
2008 Dec
[Functional and motor gastrointestinal disorders].
2008 Oct
Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.
2008 Sep
A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia.
2009 Mar
Acotiamide (Z-338) as a possible candidate for the treatment of functional dyspepsia.
2010 Jun
Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage.
2010 Jun
Patents

Patents

Sample Use Guides

In general, for adults, take 1 tablet (100mg of the active ingredient) at a time, 3 times a day before meals.
Route of Administration: Oral
Acotiamide (0.3 and 1 uM) significantly enhanced the contraction of guinea pig gastric body strips induced by electrical field stimulation
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:28:00 GMT 2025
Edited
by admin
on Mon Mar 31 18:28:00 GMT 2025
Record UNII
D42OWK5383
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ACOTIAMIDE [MI]
Preferred Name English
ACOTIAMIDE
INN   WHO-DD  
INN  
Official Name English
acotiamide [INN]
Common Name English
4-THIAZOLECARBOXAMIDE, N-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-2-((2-HYDROXY-4,5-DIMETHOXYBENZOYL)AMINO)-
Systematic Name English
Acotiamide [WHO-DD]
Common Name English
N-(2-(BIS(1-METHYLETHYL)AMINO)ETHYL)-2-((2-HYDROXY-4,5-DIMETHOXYBENZOYL)AMINO)THIAZOLE-4-CARBOXAMIDE
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C267
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
NCI_THESAURUS C47792
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
Code System Code Type Description
INN
8506
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
NCI_THESAURUS
C65214
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
ChEMBL
CHEMBL2107723
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
MERCK INDEX
m1383
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
CAS
185106-16-5
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
FDA UNII
D42OWK5383
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
PUBCHEM
5282338
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
EPA CompTox
DTXSID40870163
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
DRUG BANK
DB12482
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
WIKIPEDIA
ACOTIAMIDE
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
SMS_ID
300000036947
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
DRUG CENTRAL
4908
Created by admin on Mon Mar 31 18:28:00 GMT 2025 , Edited by admin on Mon Mar 31 18:28:00 GMT 2025
PRIMARY
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SALT/SOLVATE -> PARENT
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TARGET -> INHIBITOR
TARGET -> INHIBITOR
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ACTIVE MOIETY