MEBEVERINE

Possibly Marketed Outside US

Details

Stereochemistry	RACEMIC
Molecular Formula	C25H35NO5
Molecular Weight	429.5491
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CCCCOC(=O)C1=CC=C(OC)C(OC)=C1)C(C)CC2=CC=C(OC)C=C2

InChI

InChIKey=VYVKHNNGDFVQGA-UHFFFAOYSA-N

InChI=1S/C25H35NO5/c1-6-26(19(2)17-20-9-12-22(28-3)13-10-20)15-7-8-16-31-25(27)21-11-14-23(29-4)24(18-21)30-5/h9-14,18-19H,6-8,15-17H2,1-5H3

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/uk/mebeverine-hydrochloride-135mg-tablets-leaflet.html
Curator's Comment: description was created based on several sources, including: http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con744437.pdf | https://www.ncbi.nlm.nih.gov/pubmed/20128021

Mebeverine is an antispasmodic with a direct action on the smooth muscle of the gastrointestinal tract. The exact mechanism of action is not known, but multiple mechanisms, such as a decrease in ion channel permeabilities, blockade of noradrenaline reuptake, a local anesthetic effects, as well as weak anti-muscarinic and phosphodiesterase inhibitory effect might contribute to the local effects of Mebeverine. This medicine is used to treat symptoms of irritable bowel syndrome (IBS) and similar problems such as chronic irritable colon, spastic constipation, mucous colitis and spastic colitis. Most people will not have problems with Mebeverine, but some may get some side effects, such as: difficulty in breathing, swelling of face, neck, tongue or throat, skin rash, red itchy skin.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Alpha-1 adrenergic receptor (guinea pig) 3 Target ID: Alpha-1 adrenergic receptor (guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2442008	Inhibitor 8504
Muscarinic acetylcholine receptors (guinea pig) 3 Target ID: Muscarinic acetylcholine receptors (guinea pig) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2442008	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Irritable bowel syndrome 61 Sources: http://www.hpra.ie/img/uploaded/swedocuments/2104633.PA0108_014_001.410e2de2-8d1a-43db-bf65-5ad045a496bd.000001Product%20Leaflet%20Approved%20Colofac.130214.pdf https://www.drugs.com/uk/mebeverine-hydrochloride-135mg-tablets-leaflet.html	Palliative	Approved 8583	Colofac Approved Use Colofac is used to treat symptoms of irritable bowel syndrome and similar problems. Launch Date 1978
Mucous colitis 3 Sources: https://www.medicines.org.uk/emc/PIL.2531.latest.pdf http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con744437.pdf	Palliative	Approved 8583	Colofac Approved Use This medicine is used to treat symptoms of irritable bowel syndrome (IBS) and similar problems such as chronic irritable colon, spastic constipation, mucous colitis and spastic colitis. Launch Date 1978
Spastic constipation 3 Sources: https://www.medicines.org.uk/emc/PIL.2531.latest.pdf http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con744437.pdf	Palliative	Approved 8583	Colofac Approved Use This medicine is used to treat symptoms of irritable bowel syndrome (IBS) and similar problems such as chronic irritable colon, spastic constipation, mucous colitis and spastic colitis Launch Date 1978

C_max

Value	Dose	Analyte	Population
685.28 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
28.79 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.61 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	1-BUTANOL, 4-(ETHYL(2-(4-METHOXYPHENYL)-1-METHYLETHYL)AMINO)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
62.52 ng/mL EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
291.81 ng/mL EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
7669.41 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
339.21 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
47.57 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	1-BUTANOL, 4-(ETHYL(2-(4-METHOXYPHENYL)-1-METHYLETHYL)AMINO)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
365.85 ng × h/mL EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2551.74 ng × h/mL EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
7.39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.78 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.99 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28192719/	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	1-BUTANOL, 4-(ETHYL(2-(4-METHOXYPHENYL)-1-METHYLETHYL)AMINO)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.87 h EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.52 h EXPERIMENT https://www.mathewsopenaccess.com/full-text/the-rapid-and-sensitive-hplc-ms-ms-method-of-determination-of-mebeverine-metabolites-in-human-plasma	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	O-DESMETHYL MEBEVERINE ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Analyte	Population
16.49% EXPERIMENT https://zjps.journals.ekb.eg/article_186342.html	MEBEVERINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25.68% EXPERIMENT https://zjps.journals.ekb.eg/article_186342.html	MEBEVERINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
25% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28435220/	MEBEVERINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	Other AEs: Diarrhoea, Anorexia... Other AEs: Diarrhoea (grade 1, 1.7%) Anorexia (grade 2, 1.7%) Headache (grade 1-2, 3.3%) Menorrhagia (grade 2, 1.7%) Palpitation (grade 2, 1.7%) Alopecia (grade 1, 1.7%) Cystitis (grade 2, 3.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
50 mg single, intravenous Highest studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/	Other AEs: Faintness, Dizziness... Other AEs: Faintness (7.1%) Dizziness (14.2%) Vomiting (7.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/

AEs

AE	Significance	Dose	Population
Alopecia	grade 1, 1.7%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Diarrhoea	grade 1, 1.7%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Headache	grade 1-2, 3.3%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Anorexia	grade 2, 1.7%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Menorrhagia	grade 2, 1.7%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Palpitation	grade 2, 1.7%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Cystitis	grade 2, 3.3%	270 mg 3 times / day multiple, oral Highest studied dose Dose: 270 mg, 3 times / day Route: oral Route: multiple Dose: 270 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/8576295/
Dizziness	14.2%	50 mg single, intravenous Highest studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/
Faintness	7.1%	50 mg single, intravenous Highest studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/
Vomiting	7.1%	50 mg single, intravenous Highest studied dose Dose: 50 mg Route: intravenous Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/5318612/

PubMed

Title	Date	PubMed
Treatment patterns and health care costs of mebeverine-treated IBS patients: a case-control study.	2004 Nov	15386693
Rapid accurate mass desorption electrospray ionisation tandem mass spectrometry of pharmaceutical samples.	2005	16287035
A new RP-HPLC method for analysis of mebeverine hydrochloride in raw materials and tablets.	2005 Apr	16431391
[Abdominal migraine as a cause of chronic recurrent abdominal pain in a 9-years-old girl--case report].	2005 Aug	16245431
Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial.	2005 Aug 20	16093252
Potentiometric flow injection analysis of mebeverine hydrochloride in serum and urine.	2005 Jan 4	15620532
[Mebeverine for complex treatment of opisthorchiasis].	2006	17615648
[The pain problem as a historic aspect. Pain at the biliary pathology. Mebeverine hydrochloride as a part of complex therapy].	2006	16866271
Generic and brand-name drugs. Are different criteria sufficiently taken into account before granting market authorisation?	2006	16700151
Formulation of an antispasmodic drug as a topical local anesthetic.	2006 Dec 1	16935442
Cognitive behavioural therapy in addition to antispasmodic therapy for irritable bowel syndrome in primary care: randomised controlled trial.	2006 Jun	16729918
Investigative implications of the instability and metabolism of mebeverine.	2006 Mar	16620538
Quality of life of patients with irritable bowel syndrome is low compared to others with chronic diseases.	2006 May	16607141
"My patients are the sickest".	2006 May	16607139
Mebeverine influences sodium ion transport in the distal colon.	2006 Sep-Oct	17085870
[Assessment of the efficacy of mebeverine in the complex therapy of chronic noncalculolis cholecystitis and biliary dysfunction].	2007	17539356
Colon-specific drug delivery for mebeverine hydrochloride.	2007 Dec	18041637
Development of in situ ion selective sensors for dissolution.	2007 Jan 2	17386443
[Drug treatment of irritable bowel syndrome: an unmet need].	2007 Mar	17374325
Improving the detection limits of antispasmodic drugs electrodes by using modified membrane sensors with inner solid contact.	2007 May 9	17383844
A novel formulation for mebeverine hydrochloride.	2007 Oct	17882731
Health technology assessment and ill-structured problems: a case study concerning the drug mebeverine.	2007 Summer	17579933
[Efficacy of duspatalin in the treatment and prophylaxis of postcholecystectomic syndrome].	2008	19145887
Cost-effectiveness of cognitive behaviour therapy in addition to mebeverine for irritable bowel syndrome.	2008 Apr	18334867
Spectrophotometric determination of benzydamine HCl, levamisole HCl and mebeverine HCl through ion-pair complex formation with methyl orange.	2008 Mar	17625955
[Irritable bowel syndrome-an unbeloved problem].	2008 Mar 27	18522357
Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials.	2008 May	18242143
Drug use in children: cohort study in three European countries.	2008 Nov 24	19029175
Development of membrane selective electrode for determination of the antipsychotic sulpiride in pharmaceuticals and urine.	2009	22408528
[The effectiveness of spasmolytic therapy in chronic acalculous cholecystitis].	2009	19552029
[How to raise efficacy of gastroesophageal reflux disease treatment].	2009	19334485
Psychological associations of irritable bowel syndrome besides panic disorder: an often overlooked reality.	2009	18821173
Validated LC-MS/MS method for determination of Alverine and one of its hydroxy metabolites in human plasma along with its application to a bioequivalence study.	2009 Jan 15	19110477
pH-Sensitive Mebeverine Microspheres for Colon Delivery.	2009 Jul	20502560
The four killers of Meckel's diverticulum.	2009 May	19561979
[A method for non-medicamentous treatment of irritated bowel syndrome].	2009 May-Jun	19639692
[Modern approaches to the therapy of biliary system diseases].	2010	20623959
Predictors of treatment outcome after cognitive behavior therapy and antispasmodic treatment for patients with irritable bowel syndrome in primary care.	2010 Apr	20307706
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.	2010 Dec	21818443
A systematic review of efficacy and tolerability of mebeverine in irritable bowel syndrome.	2010 Feb 7	20128021
Validated HPLC determination of the two fixed dose combinations (chlordiazepoxide hydrochloride and mebeverine hydrochloride; carvedilol and hydrochlorothiazide) in their tablets.	2010 Jul-Aug	20922951
Design and formulation of mebeverine HCl semisolid formulations for intraorally administration.	2010 Mar	20101482
Colloids as a sink for certain pharmaceuticals in the aquatic environment.	2010 May	20024675
First derivative synchronous fluorescence spectroscopy for the simultaneous determination of sulpiride and mebeverine hydrochloride in their combined tablets and application to real human plasma.	2010 Nov	20607372
Management of irritable bowel syndrome in primary care: feasibility randomised controlled trial of mebeverine, methylcellulose, placebo and a patient self-management cognitive behavioural therapy website. (MIBS trial).	2010 Nov 18	21087463
Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream.	2010 Nov 4	21116332
Development and validation of stability indicating HPLC and HPTLC methods for determination of sulpiride and mebeverine hydrochloride in combination.	2010 Sep	20538381
Autoimmune hepatitis triggered by nitrofurantoin: a case series.	2010 Sep 23	20863377
Presentations of perforated colonic pathology in patients with polymyalgia rheumatica: two case reports.	2010 Sep 6	20819228
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

One tablet (135 mg) three times a day. This may be gradually reduced after a few weeks when the desired effect has been obtained. The tablets are best taken 20 minutes before meals.

Route of Administration: Oral

In Vitro Use Guide

Mebeverine (10^5-10^4 M) suppressed the amplitude of the action potential and lengthened the time between stimulation and the top of the response in non-myelinated fibres of the vagus nerve.

Name

Type

Language

ARLUY

Preferred Name

English

MEBEVERINE

Official Name

English

MEBEVERINE [MI]

Common Name

English

Mebeverine [WHO-DD]

Common Name

English

BENZOIC ACID, 3,4-DIMETHOXY-, 4-(ETHYL(2-(4-METHOXYPHENYL)-1-METHYLETHYL)AMINO)BUTYL ESTER

Common Name

English

VERATRIC ACID, 4-((ETHYL(P-METHOXY-.ALPHA.-METHYLPHENETHYL))AMINO)BUTYL ESTER

Common Name

English

4-(ETHYL(P-METHOXY-.ALPHA.-METHYLPHENETHYL)AMINO)BUTYL VERATRATE

Common Name

English

mebeverine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66880