ITOPRIDE HYDROCHLORIDE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H26N2O4.ClH
Molecular Weight	394.892
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=C(OC)C=C(C=C1)C(=O)NCC2=CC=C(OCCN(C)C)C=C2

InChI

InChIKey=ZTOUXLLIPWWHSR-UHFFFAOYSA-N

InChI=1S/C20H26N2O4.ClH/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);1H

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
Effect of reversible ligands on oxime-induced reactivation of sarin- and cyclosarin-inhibited human acetylcholinesterase.	2015-02-03	25522658
Effect of probiotic Lactobacillus (Lacidofil® cap) for the prevention of antibiotic-associated diarrhea: a prospective, randomized, double-blind, multicenter study.	2010-12	21165295
A Simple RP-HPLC Method for Quantitation of Itopride HCl in Tablet Dosage Form.	2010-10	21264104
Pharmacotherapy for gastroparesis: an attempt to evaluate a safer alternative.	2010-10	21103416
A case of spontaneous regression of advanced gastric cancer.	2010-10	20890436
Development and validation of a LC-MS/MS method for the determination of clebopride and its application to a pharmacokinetics study in healthy Chinese volunteers.	2010-08-01	20598654
Evaluation of anti-GERD activity of gastro retentive drug delivery system of itopride hydrochloride.	2010-08	20515421
Banha-sasim-tang as an herbal formula for the treatment of functional dyspepsia: a randomized, double-blind, placebo-controlled, two-center trial.	2010-07-30	20670451
Preclinical electrogastrography in experimental pigs.	2010-06	21217873
Idiopathic proximal hemimegacolon in an adult woman.	2010-04	20535353
Functional dyspepsia: a pragmatic approach.	2010	21180236
Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.	2010	20422945
Simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form by spectrophotometry.	2009-12-05	19957542
Acupuncture as a treatment for functional dyspepsia: design and methods of a randomized controlled trial.	2009-08-23	19698147
[Effect of prokinetic agents on the electrical activity of stomach and duodenum in rats].	2009-07	19648670
Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract.	2009-04	19220673
Tardive dyskinesia associated with long-term administration of escitalopram and itopride in major depressive disorder.	2009-03-17	19121360
Optimized method for the determination of itopride in human plasma by high-performance liquid chromatography with fluorimetric detection.	2009-03-15	19246254
Determination of itopride hydrochloride in human plasma by RP-HPLC with fluorescence detection and its use in bioequivalence study.	2009-03	19101632
Applications of nanomaterials in electrogenerated chemiluminescence biosensors.	2009	22389624
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
Itopride and pantoprazole outcomes in diabetic gastroparesis trial (IPOD trial).	2008-12	19370958
Prokinetics and fundic relaxants in upper functional GI disorders.	2008-12	18940266
Rabeto plus: a valuable drug for managing functional dyspepsia.	2008-11	19368103
Validation of 13C-acetic acid breath test by measuring effects of loperamide, morphine, mosapride, and itopride on gastric emptying in mice.	2008-10	18827355
Quantitative estimation of itopride hydrochloride and rabeprazole sodium from capsule formulation.	2008-09	21394269
Acotiamide hydrochloride (Z-338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats.	2008-09	18482254
Potentiation by cholinesterase inhibitors of cholinergic activity in rat isolated stomach and colon.	2008-08-04	18824231
Effect of itopride hydrochloride on the ileal and colonic motility in guinea pig in vitro.	2008-06-30	18581598
Pitfalls in designing trials of functional dyspepsia: the ascent and demise of itopride.	2008-06	18477673
Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials.	2008-06	17965059
Effect of itopride on gastric emptying in longstanding diabetes mellitus.	2008-05	18179609
Long-term Ultrasonographic Follow-up Study of Gastric Motility in Patients with Functional Dyspepsia.	2008-03	18385832
Spectrophotometric simultaneous determination of rabeprazole sodium and itopride hydrochloride in capsule dosage form.	2008-03	17604217
Efficacy of prokinetic agents in improving bowel preparation for colonoscopy.	2008	18577886
Mosapride in gastrointestinal disorders.	2008	18457463
Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies.	2007-09	18019739
Thermal care of functional dyspepsia based on bicarbonate-sulphate-calcium water: a sequential clinical trial.	2007-09	17965771
A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.	2007-03	17300287
Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia.	2007-03	17295758
Determination of itopride in human plasma by liquid chromatography coupled to tandem mass spectrometric detection: application to a bioequivalence study.	2007-01-30	17386535
Ergotism with ischemia in all four extremities: a case report.	2006-12	20396534
Simultaneous HPTLC Determination of Rabeprazole and Itopride Hydrochloride From Their Combined Dosage Form.	2006-11-28	20046748
[Functional dyspepsia. Itopride improves symptoms].	2006-10	17058905
Mirtazapine for severe gastroparesis unresponsive to conventional prokinetic treatment.	2006-09-09	16959934
How effective is itopride for the treatment of patients with functional dyspepsia?	2006-09	16951665
Itopride for functional dyspepsia.	2006-06-01	16738281
Effects of itopride hydrochloride on plasma gut-regulatory peptide and stress-related hormone levels in healthy human subjects.	2006	16717477
Evaluation of new gastro-intestinal prokinetic (ENGIP-II) study.	2005-12	16821670

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 HYDROCHLORIDE

Common Name

English

BENZAMIDE, N-((4-(2-(DIMETHYLAMINO)ETHOXY)PHENYL)METHYL)-3,4-DIMETHOXY-, MONOHYDROCHLORIDE

Preferred Name

English

ITOPRIDE HYDROCHLORIDE [JAN]

Common Name

English

ITOPRIDE HYDROCHLORIDE [MI]

Common Name

English

ITOPRIDE HCL

Common Name

English

Itopride hydrochloride [WHO-DD]

Common Name

English

ITOPRIDE HYDROCHLORIDE [MART.]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C47792