ITOPRIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H26N2O4
Molecular Weight	358.4314
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(C=C1OC)C(=O)NCC2=CC=C(OCCN(C)C)C=C2

InChI

InChIKey=QQQIECGTIMUVDS-UHFFFAOYSA-N

InChI=1S/C20H26N2O4/c1-22(2)11-12-26-17-8-5-15(6-9-17)14-21-20(23)16-7-10-18(24-3)19(13-16)25-4/h5-10,13H,11-12,14H2,1-4H3,(H,21,23)

HIDE SMILES / InChI

Description
Sources: https://www.rlsnet.ru/tn_index_id_36285.htm
Curator's Comment: description was created based on several sources, including http://www.meppo.com/pdf/drugs/2845-GANATON-1415104080.pdf

Itopride is a dopamine D2 receptor antagonist and inhibitor of acetylcholinesterase. It is indicated in the for the treatment of gastrointestinal symptoms caused by reduced gastrointestinal motility, such as functional non-ulcer dyspepsia (chronic gastritis), gastric fullness, rapid satiation, pain or discomfort in the upper abdomen, anorexia, heartburn, nausea, and vomiting. The drug is not approved in the USA or UK but is available in Japan and Western European countries.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 209 Target ID: P22303\|\|\|Q53F46 Gene ID: 43.0 Gene Symbol: ACHE Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7869618	Inhibitor 8504		2.04 µM [IC50]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1831229	Antagonist 2849		0.16 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Chronic gastritis 4 Sources: http://www.meppo.com/pdf/drugs/2845-GANATON-1415104080.pdf	Palliative	Approved 8583	GANATON Approved Use Gastrointestinal symptoms in chronic gastritis (bloated feeling, upper abdominal pain, anorexia, heartburn, nausea, and vomiting)
Irritable bowel syndrome 61 Sources: https://clinicaltrials.gov/ct2/show/NCT01027260	Primary	Phase II 1147	Unknown Approved Use Unknown
Gastroparesis 9 Sources: https://clinicaltrials.gov/ct2/show/NCT00370084	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
244.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
426.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
416.2 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.28 g/mL OTHER GOV'T https://getzpharma.com/wp-content/uploads/2016/07/Regasta-Tab-Leaflet-Pakistan.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	ITOPRIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
2606.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2895.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2740.5 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	150 mg 1 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
5.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470753/	50 mg 3 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	ITOPRIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
4% OTHER GOV'T https://getzpharma.com/wp-content/uploads/2016/07/Regasta-Tab-Leaflet-Pakistan.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		ITOPRIDE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
100 mg 3 times / day steady, Highest studied dose Dose: 100 mg, 3 times / day Route: steady Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16015691/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/16015691/	Sources: https://pubmed.ncbi.nlm.nih.gov/16015691/
100 mg 3 times / day steady, oral Studied dose Dose: 100 mg, 3 times / day Route: oral Route: steady Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/35357058/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/35357058/	Sources: https://pubmed.ncbi.nlm.nih.gov/35357058/
100 mg 3 times / day steady, oral Studied dose Dose: 100 mg, 3 times / day Route: oral Route: steady Dose: 100 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17965059/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/17965059/	Sources: https://pubmed.ncbi.nlm.nih.gov/17965059/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP2E1 1060 CYP1A2 2153 CYP2C19 2057 CYP2A6 879 CYP2B6 926 CYP3A5 136	FMO3 77

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2A6 911	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2B6 1160	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2C19 2141	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2C8 1117	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2C9 2497	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2E1 1146	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP3A4 2633	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP3A5 201	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	no
CYP2D6 2546	inhibitor 4027 Sources: https://ascpt.onlinelibrary.wiley.com/doi/10.1016/j.clpt.2005.12.187	yes [IC50 8.81 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
FMO3 77	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/25224784/ \| https://pubmed.ncbi.nlm.nih.gov/10997945/	yes		weak (pharmacogenomic study) Comment: AUC of itopride increased by 127.82±41.99 % (P<0.001) in homozygous FMO3 hhdd subjects (n=6) compared with the HHDD group (n=6). Sources: https://pubmed.ncbi.nlm.nih.gov/25224784/ \| https://pubmed.ncbi.nlm.nih.gov/10997945/

PubMed

Title	Date	PubMed
Establishing a comprehensive questionnaire for detecting drug-induced extrapyramidal symptoms.	2003 Oct	14577334
Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia.	2004 Dec	15871365
Chromatographic determination of itopride hydrochloride in the presence of its degradation products.	2005 Aug	16158999
Evaluation of new gastro-intestinal prokinetic (ENGIP-I) study.	2005 Oct	16498771
A placebo-controlled trial of itopride in functional dyspepsia.	2006 Feb 23	16495395
Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia.	2007 Mar	17295758
Thermal care of functional dyspepsia based on bicarbonate-sulphate-calcium water: a sequential clinical trial.	2007 Sep	17965771
Mosapride in gastrointestinal disorders.	2008	18457463
Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).	2008 Dec	19370958
Pitfalls in designing trials of functional dyspepsia: the ascent and demise of itopride.	2008 Jun	18477673
Effect of itopride on gastric emptying in longstanding diabetes mellitus.	2008 May	18179609
Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.	2008 May-Jun	20046748
Rabeto plus: a valuable drug for managing functional dyspepsia.	2008 Nov	19368103
Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated stomach and colon.	2008 Nov-Dec	18824231
Validation of 13C-acetic acid breath test by measuring effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice.	2008 Oct	18827355
Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.	2008 Sep	18482254
Pharmacokinetics and bioequivalence study of a fixed dose combination of rabeprazole and itopride in healthy Indian volunteers.	2009	19856792
[The use of prokinetics for the correction of motor and tonic digestive disorders].	2009	19469257
Acupuncture as a treatment for functional dyspepsia: design and methods of a randomized controlled trial.	2009 Aug 23	19698147
[Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].	2009 Jul	19648670
Functional dyspepsia: a pragmatic approach.	2010	21180236
Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.	2010 Aug	20515421
Effect of probiotic Lactobacillus (Lacidofil® cap) for the prevention of antibiotic-associated diarrhea: a prospective, randomized, double-blind, multicenter study.	2010 Dec	21165295
Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia: a randomized, double-blind, placebo-controlled, two-center trial.	2010 Jul 30	20670451
Pharmacotherapy for gastroparesis: an attempt to evaluate a safer alternative.	2010 Oct	21103416
A case of spontaneous regression of advanced gastric cancer.	2010 Oct	20890436

Patents

Sample Use Guides

In Vivo Use Guide

The usual adult dosage is 150mg of itopride hydrochloride (3 tablets) per oral administration daily in three divided doses before meals. The dose may be reduced according to the patient’s age and symptoms.

Route of Administration: Oral

In Vitro Use Guide

To study the interaction between itopride and D2 receptors, rat striatum homogenate was used. The striatal homogenate was incubated with [3H]spiperone (at a final concentration of 0.3 nM), 10nM ketanserin and 10M pargyline, and the displacing ligand at a final concentration from 1 pM to 100 uM. Radioactivity was measured using filtration through Whatman GF/B filters and liquid scintillation counting.

Name

Type

Language

ITOPRIDE [MI]

Preferred Name

English

ITOPRIDE

Official Name

English

N-(P-(2-(DIMETHYLAMINO)ETHOXY)BENZYL)VERATRAMIDE

Common Name

English

NSC-759643

Code

English

itopride [INN]

Common Name

English

Itopride [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47792