TRIMEBUTINE MALEATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C22H29NO5.C4H4O4
Molecular Weight	503.5415
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)\C=C/C(O)=O.CCC(COC(=O)C1=CC(OC)=C(OC)C(OC)=C1)(N(C)C)C2=CC=CC=C2

InChI

InChIKey=FSRLGULMGJGKGI-BTJKTKAUSA-N

InChI=1S/C22H29NO5.C4H4O4/c1-7-22(23(2)3,17-11-9-8-10-12-17)15-28-21(24)16-13-18(25-4)20(27-6)19(14-16)26-5;5-3(6)1-2-4(7)8/h8-14H,7,15H2,1-6H3;1-2H,(H,5,6)(H,7,8)/b;2-1-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9364286 | https://www.ncbi.nlm.nih.gov/pubmed/21725804 | http://www.aapharma.ca/downloads/en/PIL/Trimebutine_PM.pdf

Trimebutine [3,4,5-trimethoxybenzoic acid 2-(dimethylamino)-2-phenylbutylester] is a noncompetitive spasmolytic agent. The actions of trimebutine on the gastrointestinal tract are mediated via (i) an agonist effect on peripheral mu, kappa and delta opiate receptors and (ii) release of gastrointestinal peptides such as motilin and modulation of the release of other peptides, including vasoactive intestinal peptide, gastrin and glucagon. Trimebutine attenuated colonic motility mainly through the inhibition of L-type Ca(2+) channels at higher concentrations, whereas, at lower concentrations, it depolarized membrane potentials by reducing BK(ca) currents, resulting in the enhancement of the muscle contractions.Trimebutine accelerates gastric emptying, induces premature phase III of the migrating motor complex in the intestine and modulates the contractile activity of the colon. It is indicated for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Vascular cell adhesion protein 1 8 Target ID: CHEMBL3735 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28714852 \| https://www.ncbi.nlm.nih.gov/pubmed/26253722	Agonist 2678
Opioid receptors; mu/kappa/delta 33 Target ID: CHEMBL2095181 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9364286 \| https://www.ncbi.nlm.nih.gov/pubmed/1963196 \| https://www.ncbi.nlm.nih.gov/pubmed/2886594	Agonist 2678
Voltage-gated L-type calcium channel 92 Target ID: CHEMBL2095229 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21725804 \| https://www.ncbi.nlm.nih.gov/pubmed/21725819 \| https://www.ncbi.nlm.nih.gov/pubmed/2171963	Blocker 537
Calcium-activated potassium channel subunit alpha-1 25 Target ID: CHEMBL4304 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21725804 \| https://www.ncbi.nlm.nih.gov/pubmed/21725819	Blocker 537

Conditions

Condition	Modality	Targets	Highest Phase	Product
Irritable bowel syndrome 60 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26985535	Primary		Approved 8429	TRIMEBUTINE Approved Use TRIMEBUTINE (trimebutine maleate) is indicated: – for the treatment and relief of symptoms associated with the irritable bowel syndrome (spastic colon); and – in postoperative paralytic ileus in order to accelerate the resumption of the intestinal transit following abdominal surgery.
Spinal cord injury 13 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28714852	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
General pharmacology of the four gastrointestinal motility stimulants bethanechol, metoclopramide, trimebutine, and cisapride.	1991 Jun	1930352
Comparison of the effects of trimebutine and YM114 (KAE-393), a novel 5-HT3 receptor antagonist, on stress-induced defecation.	1993 Dec 7	8112388
Duodenogastric reflux following cholecystectomy in the dog: role of antroduodenal motor function.	2001 Aug	11472328
Effects of TAK-637, a novel neurokinin-1 receptor antagonist, on colonic function in vivo.	2001 Aug	11454917
[HPCE determination of trimebutine maleate in rat plasma and its pharmacokinetics].	2001 Feb	12579881
Determination of trimebutine maleate in rat plasma and tissues by using capillary zone electrophoresis.	2001 Jun	11438965
Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome.	2001 Mar	11207510
[Dysfunction of the Oddi's sphincter].	2001 Sep	11787376
Allergic contact dermatitis due to trimebutine.	2001 Sep	11553143
The role of remote gut inflammation in duodenojejunal dysmotility.	2002 Apr	11975714
[Prokinetics of gastrointestinal system; its newer aspects with regard to motillity stimulants].	2002 Feb	11979811
Oesophageal motility disorders.	2002 Jan 12	11809295
Efficacy of trimebutine therapy in patients with gastroesophageal reflux disease and irritable bowel syndrome.	2002 Jan-Feb	11941952
Centrally acting agents and visceral sensitivity.	2002 Jul	12077076
Laxative and anti-diarrheal activity of polycarbophil in mice and rats.	2002 Jun	12120755
[Physicochemical and pharmacological characteristic and clinical efficacy of an anti-irritable bowel syndrome agent, polycarbophil calcium (Polyful)].	2002 Mar	11915521
Quantitative determination of trimebutine maleate and its three metabolites in human plasma by liquid chromatography-tandem mass spectrometry.	2002 Nov 5	12361732
Preparation, characterization and taste-masking properties of polyvinylacetal diethylaminoacetate microspheres containing trimebutine.	2002 Oct	12396292
Spectrophotometric and liquid chromatographic determination of trimebutine maleate in the presence of its degradation products.	2003 Sep 19	12972088
Beneficial effect of trimebutine and N-monodesmethyl trimebutine on trinitrobenzene sulfonic acid-induced colitis in rats.	2004 Dec 3	15531383
Delayed reaction urticaria due to trimebutine.	2004 Jul	15180771
H pylori infection and reflux oesophagitis.	2004 Jun	15138222
[Pharmacokinetics and bioequivalence of trimebutine dispersive tablet in healthy subjects].	2004 Mar	15171657
[Abdominal migraine as a cause of chronic recurrent abdominal pain in a 9-years-old girl--case report].	2005 Aug	16245431
Novelty stress increases fecal pellet output in mongolian gerbils: effects of several drugs.	2005 Aug	16079466
Determination of trimebutine in pharmaceuticals by differential pulse voltammetry at a glassy carbon electrode.	2005 Jul 15	15967289
Rectal instillation of butyrate provides a novel clinically relevant model of noninflammatory colonic hypersensitivity in rats.	2005 Jun	15940632
Effect of nor-trimebutine on neuronal activation induced by a noxious stimulus or an acute colonic inflammation in the rat.	2005 Oct 21	15978629
Prokinetic agents in childen with poor appetite.	2005 Oct-Dec	16432992
Pharmacokinetic study of trimebutine maleate in rabbit blood using in vivo microdialysis coupled to capillary electrophoresis.	2005 Sep 15	15939564
The effect of trimebutine on the psychosocial adjustment to illness in the irritable bowel syndrome.	2006	18386606
Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine: a double-blind, randomized, cross-over, placebo-controlled study.	2006 Jul	16776704
Increasing the effect of triptans in migraine.	2006 Oct 14	17046449
The use of combination therapies in the acute management of migraine.	2006 Sep	19412476
Spectrophotometric determination of some anti-tussive and anti-spasmodic drugs through ion-pair complex formation with thiocyanate and cobalt(II) or molybdenum(V).	2007 Apr	17142094
Pharmacokinetic and bioequivalence evaluation of two formulations of 100 mg trimebutine maleate (Recutin and Polybutin) in healthy male volunteers using the LC-MS/MS method.	2007 Jan	16854404
[Drug treatment of irritable bowel syndrome: an unmet need].	2007 Mar	17374325
Meta-analysis of the effects of prokinetic agents in patients with functional dyspepsia.	2007 Mar	17295758
[A randomized and case-control clinical study on trimebutine maleate in treating functional dyspepsia coexisting with diarrhea-dominant irritable bowel syndrome].	2007 Nov	18261269
Treatment of functional dyspepsia with serotonin agonists: a meta-analysis of randomized controlled trials.	2007 Oct	17845684
Inhibitory effects of ramosetron, a potent and selective 5-HT3-receptor antagonist, on conditioned fear stress-induced abnormal defecation and normal defecation in rats: comparative studies with antidiarrheal and spasmolytic agents.	2008 Feb	18296863
Effects of serotonin 5-HT3 receptor antagonists on stress-induced colonic hyperalgesia and diarrhoea in rats: a comparative study with opioid receptor agonists, a muscarinic receptor antagonist and a synthetic polymer.	2008 May	18221252
Effect of four medications associated with gastrointestinal motility on Oddi sphincter in the rabbit.	2009	19657216
Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract.	2009 Apr	19220673
A nitro-arginine derivative of trimebutine (NO2-Arg-Trim) attenuates pain induced by colorectal distension in conscious rats.	2009 May	19416632
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
[Prokinetics in childhood].	2010 Jun	20654867
Effectiveness of trimebutine maleate on modulating intestinal hypercontractility in a mouse model of postinfectious irritable bowel syndrome.	2010 Jun 25	20371236
Risk factors of drug interaction between warfarin and nonsteroidal anti-inflammatory drugs in practical setting.	2010 Mar	20191029
Development of a novel combination tablet containing trimebutine maleate and mosapride citrate for the treatment of functional dyspepsia.	2010 Nov 15	20826201

Patents

Sample Use Guides

In Vivo Use Guide

The adult recommended dose is up to 600 mg daily in divided doses. It may be administered as two 100 mg tablets three times daily before meals or one 200 mg tablet three times daily before meals.

Route of Administration: Oral

In Vitro Use Guide

0.1 mM trimebutine inhibits proliferation of human LOVO colon cancer cells.

Name

Type

Language

TRIMEBUTINE MALEATE

Common Name

English

TRIMEBUTINE MALEATE [JAN]

Common Name

English

TRIMEBUTINE MALEATE [MI]

Common Name

English

2-DIMETHYLAMINO-2-PHENYLBUTYL 3,4,5-TRIMETHOXYBENZOATE HYDROGEN MALEATE

Systematic Name

English

TRIMEBUTINE MALEATE SALT

Common Name

English

Trimebutine maleate [WHO-DD]

Common Name

English

NSC-758900

Code

English

TRIMEBUTINE MALEATE [EP MONOGRAPH]

Common Name

English

TRIMEBUTINE MALEATE [MART.]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID5046017