Itopride

Synonyms :
N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide

Status : investigational

Therapeutic Classification

PROPULSIVES

ALIMENTARY TRACT AND METABOLISM
DRUGS FOR FUNCTIONAL GASTROINTESTINAL DISORDERS
PROPULSIVES

Description

Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory actions.

Used

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

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.

Metabolism

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

Chemical Classification

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.

N-benzylbenzamides

Organic compounds

Benzenoids

Benzene and substituted derivatives

Benzamides

Chemical Name

N-(p-(2-(Dimethylamino)ethoxy)benzyl)veratramide

Drug Drug Interactions

  •  Aclidinium  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Amitriptyline  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Amoxapine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Atropine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Azelastine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Benzatropine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Brompheniramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Carbinoxamine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Cetirizine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Chlorphenamine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Chlorpromazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Clemastine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Clidinium  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Clomipramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Clozapine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Codeine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Cyclizine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Cyclobenzaprine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Cyclopentolate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Cyproheptadine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Darifenacin  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Desipramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Desloratadine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Dexbrompheniramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Dicyclomine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Difenoxin  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Dimenhydrinate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Diphenhydramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Diphenoxylate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Disopyramide  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Doxepin  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Doxylamine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Droperidol  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Fenoterol  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Fesoterodine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Fexofenadine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Flavoxate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Flupentixol  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Fluphenazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Fluticasone Propionate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Glycopyrrolate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Haloperidol  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Hydroxyzine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Hyoscyamine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Imipramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Ipratropium bromide  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Isocarboxazid  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Levocabastine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Levocetirizine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Loratadine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Loxapine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Maprotiline  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Meclizine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Mepenzolate  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Methotrimeprazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Moclobemide  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Nortriptyline  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Olanzapine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Olopatadine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Orphenadrine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Oxybutynin  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Perphenazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Phenelzine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Pimozide  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Pizotifen  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Prochlorperazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Procyclidine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Promazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Promethazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Propantheline  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Protriptyline  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Quetiapine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Risperidone  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Scopolamine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Solifenacin  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Thioridazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Thiothixene  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Tiotropium  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Tolterodine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Tranylcypromine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Trifluoperazine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Trihexyphenidyl  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Trimethobenzamide  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Trimipramine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Triprolidine  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Trospium  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Umeclidinium  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.
  •  Zuclopenthixol  : Anticholinergic Agents may diminish the therapeutic effect of Itopride.

Calculated Property

kind Value Source
logP 2.41 ALOGPS
logS -4.1 ALOGPS
Water Solubility 2.61e-02 g/l ALOGPS
logP 2.32 ChemAxon
IUPAC Name N-({4-[2-(dimethylamino)ethoxy]phenyl}methyl)-3,4-dimethoxybenzamide ChemAxon
Traditional IUPAC Name itopride ChemAxon
Molecular Weight 358.4314 ChemAxon
Monoisotopic Weight 358.18925733 ChemAxon
SMILES COC1=C(OC)C=C(C=C1)C(=O)NCC1=CC=C(OCCN(C)C)C=C1 ChemAxon
Molecular Formula C20H26N2O4 ChemAxon
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) ChemAxon
InChIKey InChIKey=QQQIECGTIMUVDS-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 60.03 ChemAxon
Refractivity 102.05 ChemAxon
Polarizability 40.41 ChemAxon
Rotatable Bond Count 9 ChemAxon
H Bond Acceptor Count 5 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest acidic) 14.71 ChemAxon
pKa (strongest basic) 8.77 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 2 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • D(2) dopamine receptor : in Human
  • Muscarinic acetylcholine receptor M3 : in Human