Itopride

Identification

Name
Itopride
Accession Number
DB04924
Type
Small Molecule
Groups
Investigational
Description

Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.

Structure
Thumb
Synonyms
  • N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide
International/Other Brands
Itax
Categories
UNII
81BMQ80QRL
CAS number
122898-67-3
Weight
Average: 358.4314
Monoisotopic: 358.18925733
Chemical Formula
C20H26N2O4
InChI Key
QQQIECGTIMUVDS-UHFFFAOYSA-N
InChI
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)
IUPAC Name
N-({4-[2-(dimethylamino)ethoxy]phenyl}methyl)-3,4-dimethoxybenzamide
SMILES
COC1=C(OC)C=C(C=C1)C(=O)NCC1=CC=C(OCCN(C)C)C=C1

Pharmacology

Indication

Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders. Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. These effects appear to result from suppression of ACh release from the myenteric motor neurons and are mediated by the D2 subtype of dopamine receptors. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release. It also inhibits the enzyme AchE which prevents the degradation of ACh. The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination. This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.

TargetActionsOrganism
UD(2) dopamine receptorNot AvailableHuman
UMuscarinic acetylcholine receptor M3Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Flavin-containing monooxygenase (FMO) is involved in N-oxygenation, the major metabolic pathway of itopride (PMID: 10997945).

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AclidiniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Aclidinium.Approved
AlcuroniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Alcuronium.Experimental
Anisotropine MethylbromideThe therapeutic efficacy of Itopride can be decreased when used in combination with Anisotropine Methylbromide.Approved
AtracuriumThe therapeutic efficacy of Itopride can be decreased when used in combination with Atracurium.Experimental, Investigational
Atracurium besylateThe therapeutic efficacy of Itopride can be decreased when used in combination with Atracurium besylate.Approved
AtropineThe therapeutic efficacy of Itopride can be decreased when used in combination with Atropine.Approved, Vet Approved
BenactyzineThe therapeutic efficacy of Itopride can be decreased when used in combination with Benactyzine.Withdrawn
BenzatropineThe therapeutic efficacy of Itopride can be decreased when used in combination with Benzatropine.Approved
BiperidenThe therapeutic efficacy of Itopride can be decreased when used in combination with Biperiden.Approved, Investigational
BornaprineThe therapeutic efficacy of Itopride can be decreased when used in combination with Bornaprine.Experimental
ButylscopolamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Butylscopolamine.Approved, Vet Approved
ChlorphenoxamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Chlorphenoxamine.Withdrawn
CyclopentolateThe therapeutic efficacy of Itopride can be decreased when used in combination with Cyclopentolate.Approved
DarifenacinThe therapeutic efficacy of Itopride can be decreased when used in combination with Darifenacin.Approved, Investigational
DesloratadineThe therapeutic efficacy of Itopride can be decreased when used in combination with Desloratadine.Approved, Investigational
DexetimideThe therapeutic efficacy of Itopride can be decreased when used in combination with Dexetimide.Withdrawn
DicyclomineThe therapeutic efficacy of Itopride can be decreased when used in combination with Dicyclomine.Approved
EmeproniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Emepronium.Experimental
EtanautineThe therapeutic efficacy of Itopride can be decreased when used in combination with Etanautine.Experimental
EthopropazineThe therapeutic efficacy of Itopride can be decreased when used in combination with Ethopropazine.Approved
EtybenzatropineThe therapeutic efficacy of Itopride can be decreased when used in combination with Etybenzatropine.Experimental
FesoterodineThe therapeutic efficacy of Itopride can be decreased when used in combination with Fesoterodine.Approved
GallamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Gallamine.Experimental
Gallamine TriethiodideThe therapeutic efficacy of Itopride can be decreased when used in combination with Gallamine Triethiodide.Approved
GlycopyrroniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Glycopyrronium.Approved, Investigational, Vet Approved
HexamethoniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Hexamethonium.Experimental
HomatropineThe therapeutic efficacy of Itopride can be decreased when used in combination with Homatropine.Approved
HyoscyamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Hyoscyamine.Approved
Ipratropium bromideThe therapeutic efficacy of Itopride can be decreased when used in combination with Ipratropium bromide.Approved
MazaticolThe therapeutic efficacy of Itopride can be decreased when used in combination with Mazaticol.Experimental
MecamylamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Mecamylamine.Approved
MethanthelineThe therapeutic efficacy of Itopride can be decreased when used in combination with Methantheline.Approved, Investigational
MethscopolamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Methscopolamine.Approved
Methylscopolamine bromideThe therapeutic efficacy of Itopride can be decreased when used in combination with Methylscopolamine bromide.Approved
MetixeneThe therapeutic efficacy of Itopride can be decreased when used in combination with Metixene.Approved
OrphenadrineThe therapeutic efficacy of Itopride can be decreased when used in combination with Orphenadrine.Approved
OtiloniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Otilonium.Experimental, Investigational
OxitropiumThe therapeutic efficacy of Itopride can be decreased when used in combination with Oxitropium.Investigational
OxybutyninThe therapeutic efficacy of Itopride can be decreased when used in combination with Oxybutynin.Approved, Investigational
OxyphenoniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Oxyphenonium.Approved
PancuroniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Pancuronium.Approved
PentoliniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Pentolinium.Approved
PhenglutarimideThe therapeutic efficacy of Itopride can be decreased when used in combination with Phenglutarimide.Experimental
PipecuroniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Pipecuronium.Approved
PirenzepineThe therapeutic efficacy of Itopride can be decreased when used in combination with Pirenzepine.Approved
ProcyclidineThe therapeutic efficacy of Itopride can be decreased when used in combination with Procyclidine.Approved
PropanthelineThe therapeutic efficacy of Itopride can be decreased when used in combination with Propantheline.Approved
PropiverineThe therapeutic efficacy of Itopride can be decreased when used in combination with Propiverine.Approved, Investigational
QuinidineThe therapeutic efficacy of Itopride can be decreased when used in combination with Quinidine.Approved
ScopolamineThe therapeutic efficacy of Itopride can be decreased when used in combination with Scopolamine.Approved
SolifenacinThe therapeutic efficacy of Itopride can be decreased when used in combination with Solifenacin.Approved
TiotropiumThe therapeutic efficacy of Itopride can be decreased when used in combination with Tiotropium.Approved
TolterodineThe therapeutic efficacy of Itopride can be decreased when used in combination with Tolterodine.Approved, Investigational
TrihexyphenidylThe therapeutic efficacy of Itopride can be decreased when used in combination with Trihexyphenidyl.Approved
TrimethaphanThe therapeutic efficacy of Itopride can be decreased when used in combination with Trimethaphan.Approved, Investigational
TropatepineThe therapeutic efficacy of Itopride can be decreased when used in combination with Tropatepine.Experimental
TropicamideThe therapeutic efficacy of Itopride can be decreased when used in combination with Tropicamide.Approved
TrospiumThe therapeutic efficacy of Itopride can be decreased when used in combination with Trospium.Approved
TubocurarineThe therapeutic efficacy of Itopride can be decreased when used in combination with Tubocurarine.Approved
UmeclidiniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Umeclidinium.Approved
VecuroniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Vecuronium.Approved
Food Interactions
Not Available

References

General References
  1. Mushiroda T, Douya R, Takahara E, Nagata O: The involvement of flavin-containing monooxygenase but not CYP3A4 in metabolism of itopride hydrochloride, a gastroprokinetic agent: comparison with cisapride and mosapride citrate. Drug Metab Dispos. 2000 Oct;28(10):1231-7. [PubMed:10997945]
  2. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C: A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006 Feb 23;354(8):832-40. [PubMed:16495395]
  3. Choung RS, Talley NJ, Peterson J, Camilleri M, Burton D, Harmsen WS, Zinsmeister AR: 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. Neurogastroenterol Motil. 2007 Mar;19(3):180-7. [PubMed:17300287]
  4. Chiba T, Tokunaga Y, Ikeda K, Takagi R, Chishima R, Terui T, Kudara N, Endo M, Inomata M, Orii S, Suzuki K: Effects of itopride hydrochloride and ranitidine in patients with functional dyspepsia: comparison between prokinetic and acid suppression therapies. Hepatogastroenterology. 2007 Sep;54(78):1878-81. [PubMed:18019739]
  5. Kim YS, Kim TH, Choi CS, Shon YW, Kim SW, Seo GS, Nah YH, Choi MG, Choi SC: Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study. World J Gastroenterol. 2005 Jul 21;11(27):4210-4. [PubMed:16015691]
  6. Talley NJ, Tack J, Ptak T, Gupta R, Giguere M: Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008 Jun;57(6):740-6. Epub 2007 Oct 26. [PubMed:17965059]
External Links
PubChem Compound
3792
PubChem Substance
175426905
ChemSpider
3660
ChEBI
94809
ChEMBL
CHEMBL2107457
PharmGKB
PA152432599
ATC Codes
A03FA07 — Itopride

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentGastroparesis1
1, 2CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentIrritable Bowel Syndrome (IBS)1
2CompletedTreatmentOccasional Constipation1
2, 3CompletedTreatmentFunctional Dyspepsia1
2, 3CompletedTreatmentHealthy Volunteers1
3CompletedDiagnosticBowel preparation therapy / Colonoscopy1
3CompletedTreatmentHeartburn1
3CompletedTreatmentIndigestion2
Not AvailableCompletedTreatmentFunctional Dyspepsia1
Not AvailableUnknown StatusTreatmentFunctional Dyspepsia / Gastric Accommodation / Gastric Emptying1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0261 mg/mLALOGPS
logP2.41ALOGPS
logP2.32ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)14.71ChemAxon
pKa (Strongest Basic)8.77ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.03 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity102.05 m3·mol-1ChemAxon
Polarizability40.41 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9875
Blood Brain Barrier+0.7745
Caco-2 permeable+0.7008
P-glycoprotein substrateSubstrate0.6877
P-glycoprotein inhibitor IInhibitor0.6106
P-glycoprotein inhibitor IINon-inhibitor0.5969
Renal organic cation transporterNon-inhibitor0.625
CYP450 2C9 substrateNon-substrate0.7282
CYP450 2D6 substrateNon-substrate0.5928
CYP450 3A4 substrateSubstrate0.7453
CYP450 1A2 substrateNon-inhibitor0.8878
CYP450 2C9 inhibitorNon-inhibitor0.8754
CYP450 2D6 inhibitorNon-inhibitor0.8939
CYP450 2C19 inhibitorNon-inhibitor0.8792
CYP450 3A4 inhibitorNon-inhibitor0.7897
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7994
Ames testNon AMES toxic0.7192
CarcinogenicityNon-carcinogens0.772
BiodegradationNot ready biodegradable0.9118
Rat acute toxicity2.3307 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9678
hERG inhibition (predictor II)Non-inhibitor0.5766
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0209000000-837236e5a2af3eba7742

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-benzylbenzamides. These are compounds containing a benzamide moiety that is N-linked to a benzyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
N-benzylbenzamides
Alternative Parents
Dimethoxybenzenes / Phenoxy compounds / Benzoyl derivatives / Anisoles / Alkyl aryl ethers / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
N-benzylbenzamide / O-dimethoxybenzene / Dimethoxybenzene / Phenoxy compound / Anisole / Benzoyl / Phenol ether / Methoxybenzene / Alkyl aryl ether / Amino acid or derivatives
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Choung RS, Talley NJ, Peterson J, Camilleri M, Burton D, Harmsen WS, Zinsmeister AR: 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. Neurogastroenterol Motil. 2007 Mar;19(3):180-7. [PubMed:17300287]
  2. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C: A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006 Feb 23;354(8):832-40. [PubMed:16495395]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Choung RS, Talley NJ, Peterson J, Camilleri M, Burton D, Harmsen WS, Zinsmeister AR: 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. Neurogastroenterol Motil. 2007 Mar;19(3):180-7. [PubMed:17300287]

Drug created on October 21, 2007 16:23 / Updated on December 01, 2017 15:34