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Identification
NameItopride
Accession NumberDB04924
TypeSmall Molecule
GroupsInvestigational
DescriptionItopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.
Structure
Thumb
Synonyms
N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ItaxNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII81BMQ80QRL
CAS number122898-67-3
WeightAverage: 358.4314
Monoisotopic: 358.18925733
Chemical FormulaC20H26N2O4
InChI KeyQQQIECGTIMUVDS-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
IndicationInvestigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of actionItopride 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
D(2) dopamine receptorProteinunknownNot AvailableHumanP14416 details
Muscarinic acetylcholine receptor M3ProteinunknownNot AvailableHumanP20309 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

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

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AclidiniumThe therapeutic efficacy of Itopride can be decreased when used in combination with Aclidinium.Approved
Anisotropine MethylbromideThe therapeutic efficacy of Itopride can be decreased when used in combination with Anisotropine Methylbromide.Approved
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
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
EthopropazineThe therapeutic efficacy of Itopride can be decreased when used in combination with Ethopropazine.Approved
FesoterodineThe therapeutic efficacy of Itopride can be decreased when used in combination with Fesoterodine.Approved
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
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
MetixeneThe therapeutic efficacy of Itopride can be decreased when used in combination with Metixene.Approved
N-butylscopolammonium bromideThe therapeutic efficacy of Itopride can be decreased when used in combination with N-butylscopolammonium bromide.Vet Approved
NVA237The therapeutic efficacy of Itopride can be decreased when used in combination with NVA237.Investigational
OrphenadrineThe therapeutic efficacy of Itopride can be decreased when used in combination with Orphenadrine.Approved
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
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.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
Scopolamine butylbromideThe therapeutic efficacy of Itopride can be decreased when used in combination with Scopolamine butylbromide.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
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 InteractionsNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesA03FA07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-benzylbenzamides
Alternative Parents
Substituents
  • N-benzylbenzamide
  • O-dimethoxybenzene
  • Dimethoxybenzene
  • Benzoic acid or derivatives
  • Methoxybenzene
  • Phenylmethylamine
  • Phenol ether
  • Benzylamine
  • Benzoyl
  • Anisole
  • Alkyl aryl ether
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot 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
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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
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 ]
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Drug created on October 21, 2007 16:23 / Updated on August 17, 2016 12:24