Identification
- Summary
Itopride is an acetylcholine esterase inhibitor and dopamine D2 receptor antagonist used to treat symptoms of functional dyspepsia such as nausea and vomiting.
- Generic Name
- Itopride
- DrugBank Accession Number
- DB04924
- Background
Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Itopride (DB04924)
- Weight
- Average: 358.4314
Monoisotopic: 358.18925733 - Chemical Formula
- C20H26N2O4
- Synonyms
- Itopride
- N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide
Pharmacology
- Indication
Investigated for use/treatment in gastrointestinal diseases and disorders (miscellaneous).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Abdominal pain •••••••••••• •••••• Management of Anorexia •••••••••••• •••••• ••••••• ••••••• •••• •••••• Symptomatic treatment of Dyspepsia •••••••••••• •••••• ••••••• ••••••• •••• •••••• Symptomatic treatment of Dyspepsia •••••••••••• •••••• Symptomatic treatment of Functional dyspepsia •••••••••••• •••••• ••••••• ••••••• •••• •••••• - Contraindications & Blackbox Warnings
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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.
Target Actions Organism UDopamine D2 receptor Not Available Humans UAcetylcholinesterase inhibitorHumans - 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
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Products
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Ingredient UNII CAS InChI Key Itopride hydrochloride 2H9NV66W0I 122892-31-3 ZTOUXLLIPWWHSR-UHFFFAOYSA-N - International/Other Brands
- Ganaton / Itax / Itogard / Itomed
Categories
- ATC Codes
- A03FA07 — Itopride
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- 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
- Alkyl aryl ether / Amine / Amino acid or derivatives / Anisole / Aromatic homomonocyclic compound / Benzoyl / Carboxamide group / Carboxylic acid derivative / Dimethoxybenzene / Ether show 15 more
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 81BMQ80QRL
- CAS number
- 122898-67-3
- 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
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- PubChem Compound
- 3792
- PubChem Substance
- 175426905
- ChemSpider
- 3660
- ChEBI
- 94809
- ChEMBL
- CHEMBL2107457
- ZINC
- ZINC000000537874
- PharmGKB
- PA152432599
- Wikipedia
- Itopride
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Other Dyspepsia 1 4 Completed Other Dyspepsia / Postprandial Fullness Syndrome 1 4 Recruiting Treatment Dyspepsia 1 4 Recruiting Treatment Dyspepsia / Irritable Bowel Syndrome With Constipation (IBS-C) 1 3 Completed Diagnostic Bowel preparation therapy / Colonoscopy 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 50.000 mg Tablet Oral Tablet, film coated Oral 50 mg Tablet Oral 50 mg Tablet Oral 50.00 mg Tablet, coated Oral 50 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0261 mg/mL ALOGPS logP 2.41 ALOGPS logP 2.32 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 14.71 Chemaxon pKa (Strongest Basic) 8.77 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 60.03 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 102.05 m3·mol-1 Chemaxon Polarizability 40.58 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9875 Blood Brain Barrier + 0.7745 Caco-2 permeable + 0.7008 P-glycoprotein substrate Substrate 0.6877 P-glycoprotein inhibitor I Inhibitor 0.6106 P-glycoprotein inhibitor II Non-inhibitor 0.5969 Renal organic cation transporter Non-inhibitor 0.625 CYP450 2C9 substrate Non-substrate 0.7282 CYP450 2D6 substrate Non-substrate 0.5928 CYP450 3A4 substrate Substrate 0.7453 CYP450 1A2 substrate Non-inhibitor 0.8878 CYP450 2C9 inhibitor Non-inhibitor 0.8754 CYP450 2D6 inhibitor Non-inhibitor 0.8939 CYP450 2C19 inhibitor Non-inhibitor 0.8792 CYP450 3A4 inhibitor Non-inhibitor 0.7897 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7994 Ames test Non AMES toxic 0.7192 Carcinogenicity Non-carcinogens 0.772 Biodegradation Not ready biodegradable 0.9118 Rat acute toxicity 2.3307 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9678 hERG inhibition (predictor II) Non-inhibitor 0.5766
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 185.29663 predictedDeepCCS 1.0 (2019) [M+H]+ 187.65465 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.60832 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- 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. [Article]
- 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. [Article]
- 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
- 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. [Article]
Drug created at October 21, 2007 22:23 / Updated at June 09, 2021 08:40