Itopride

Identification

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Name
Itopride
Accession Number
DB04924
Type
Small Molecule
Groups
Investigational
Description

Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.

Structure
Thumb
Synonyms
  • Itopride
  • N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide
Product Ingredients
IngredientUNIICASInChI Key
Itopride hydrochloride2H9NV66W0I122892-31-3ZTOUXLLIPWWHSR-UHFFFAOYSA-N
International/Other Brands
Ganaton / Itax / Itogard / Itomed
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=CC=C(C=C1OC)C(=O)NCC1=CC=C(OCCN(C)C)C=C1

Pharmacology

Indication

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

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 AvailableHumans
UAcetylcholinesterase
inhibitor
Humans
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
Not Available
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
Wikipedia
Itopride
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
3CompletedTreatmentIndigestion4
Not AvailableCompletedTreatmentFunctional Dyspepsia1
Not AvailableRecruitingTreatmentCritically-ill Patients1
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
Polarizability40.58 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
Humans
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
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 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 June 04, 2019 06:13