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Identification
NameMebendazole
Accession NumberDB00643  (APRD01086)
TypeSmall Molecule
GroupsApproved, Vet Approved
Description

A benzimidazole that acts by interfering with carbohydrate metabolism and inhibiting polymerization of microtubules. [PubChem]

Structure
Thumb
Synonyms
(5-benzoyl-1H-benzimidazol-2-yl)-carbamic acid methyl ester
MBDZ
Mebendazol
Mebendazol
Mébendazole
Mebendazolum
Vermox
External Identifiers
  • R 17635
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Vermox Tablets 100 mgtablet100 mgoralJanssen Inc1982-12-31Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Emvermtablet, chewable100 mg/1oralAmedra Pharmaceuticals LLC2016-02-15Not applicableUs
Mebendazoletablet, chewable100 mg/1oralPhysicians Total Care, Inc.1996-04-04Not applicableUs
Mebendazoletablet, chewable100 mg/1oralbryant ranch prepack2010-04-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LomperEsteve
MeberixAversi
MebexCipla
MebezolJohnson
MebfilFourrts Laboratories
MebutarAndromaco
MebzolJulphar
MendazoleGlaxoSmithKline
MezoleYuan Chou
MinyoozoleEmil
MopenLi Taka Pharmaceuticals
MultielminOsorio de Moraes
NecaminAché
OvexMcNeil
PanamoxJayson
PantelminJanssen
TesicalSintesina
ThelmoxRemedica
TicoquerRoot
VermoxBiotech
Brand mixturesNot Available
SaltsNot Available
Categories
UNII81G6I5V05I
CAS number31431-39-7
WeightAverage: 295.2927
Monoisotopic: 295.095691297
Chemical FormulaC16H13N3O3
InChI KeyInChIKey=OPXLLQIJSORQAM-UHFFFAOYSA-N
InChI
InChI=1S/C16H13N3O3/c1-22-16(21)19-15-17-12-8-7-11(9-13(12)18-15)14(20)10-5-3-2-4-6-10/h2-9H,1H3,(H2,17,18,19,21)
IUPAC Name
methyl N-(6-benzoyl-1H-1,3-benzodiazol-2-yl)carbamate
SMILES
COC(=O)NC1=NC2=C(N1)C=C(C=C2)C(=O)C1=CC=CC=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzophenones
Direct ParentBenzophenones
Alternative Parents
Substituents
  • Benzophenone
  • Benzimidazole
  • Acetophenone
  • Aryl ketone
  • Benzoyl
  • Aminoimidazole
  • Heteroaromatic compound
  • Imidazole
  • Azole
  • Ketone
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (common roundworm), Ancylostoma duodenale (common hookworm), Necator americanus (American hookworm) in single or mixed infections.
PharmacodynamicsMebendazole is a (synthetic) broad-spectrum anthelmintic. The principal mode of action for Mebendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.
Mechanism of actionMebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies.
Related Articles
AbsorptionPoorly absorbed (approximately 5 to 10%) from gastrointestinal tract. Fatty food increases absorption.
Volume of distributionNot Available
Protein binding90-95%
Metabolism

Primarily hepatic. Primary metabolite is 2-amino-5-benzoylbenzimidazole, but also metabolized to inactive hydroxy and hydroxyamino metabolites. All metabolites are devoid of anthelmintic activity.

SubstrateEnzymesProduct
Mebendazole
Not Available
2-amino-5-benzoylbenzimidazoleDetails
Route of eliminationIn man, approximately 2% of administered mebendazole is excreted in urine and the remainder in the feces as unchanged drug or a primary metabolite.
Half life2.5 to 5.5 hours (range 2.5 to 9 hours) in patients with normal hepatic function. Approximately 35 hours in patients with impaired hepatic function (cholestasis).
ClearanceNot Available
ToxicityAcute oral toxicity (LD50): 620 mg/kg [Mouse]. Symptoms of overdose include elevated liver enzymes, headaches, hair loss, low levels of white blood cells (neutropenia), fever, and itching.
Affected organisms
  • Helminthic Microorganisms
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9932
Blood Brain Barrier+0.9261
Caco-2 permeable+0.7261
P-glycoprotein substrateNon-substrate0.6073
P-glycoprotein inhibitor IInhibitor0.5844
P-glycoprotein inhibitor IIInhibitor0.7534
Renal organic cation transporterNon-inhibitor0.8464
CYP450 2C9 substrateNon-substrate0.749
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6532
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6779
Ames testAMES toxic0.7212
CarcinogenicityNon-carcinogens0.9102
BiodegradationNot ready biodegradable0.994
Rat acute toxicity2.5855 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9515
hERG inhibition (predictor II)Non-inhibitor0.8028
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Teva pharmaceuticals usa
  • Mcneil pediatrics
Packagers
Dosage forms
FormRouteStrength
Tablet, chewableoral100 mg/1
Tabletoral100 mg
Prices
Unit descriptionCostUnit
Mebendazole 100 mg Chew Tabs16.42USD tab
Mebendazole 100 mg tablet chew5.32USD tablet
Mebendazole powder5.03USD g
Vermox 100 mg Chewable Tablet4.14USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point288.5 °CPhysProp
water solubility71.3 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.83SANGSTER (1994)
logS-3.88ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0387 mg/mLALOGPS
logP2.95ALOGPS
logP3.26ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)8.44ChemAxon
pKa (Strongest Basic)3.93ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area84.08 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity81.5 m3·mol-1ChemAxon
Polarizability31.1 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,657,267.

General References
  1. Link [Link]
External Links
ATC CodesP02CA01P02CA51
AHFS Codes
  • 08:08.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (72.8 KB)
Interactions
Drug Interactions
Drug
CarbamazepineThe serum concentration of Mebendazole can be decreased when it is combined with Carbamazepine.
ChloroquineThe serum concentration of Mebendazole can be decreased when it is combined with Chloroquine.
CimetidineThe serum concentration of Mebendazole can be increased when it is combined with Cimetidine.
FosphenytoinThe serum concentration of Mebendazole can be decreased when it is combined with Fosphenytoin.
MetronidazoleThe risk or severity of adverse effects can be increased when Mebendazole is combined with Metronidazole.
PhenytoinThe serum concentration of Mebendazole can be decreased when it is combined with Phenytoin.
Food Interactions
  • Lipid rich meals may improve absorption.
  • Take with food.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Structural molecule activity
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name:
TUBA1A
Uniprot ID:
Q71U36
Molecular Weight:
50135.25 Da
References
  1. Lubega GW, Geary TG, Klein RD, Prichard RK: Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and mebendazole. Mol Biochem Parasitol. 1993 Dec;62(2):281-92. [PubMed:8139621 ]
  2. MacDonald LM, Armson A, Thompson AR, Reynoldson JA: Characterisation of benzimidazole binding with recombinant tubulin from Giardia duodenalis, Encephalitozoon intestinalis, and Cryptosporidium parvum. Mol Biochem Parasitol. 2004 Nov;138(1):89-96. [PubMed:15500920 ]
  3. Oxberry ME, Gear TG, Prichard RK: Assessment of benzimidazole binding to individual recombinant tubulin isotypes from Haemonchus contortus. Parasitology. 2001 Jun;122(Pt 6):683-7. [PubMed:11444621 ]
  4. Ochola DO, Prichard RK, Lubega GW: Classical ligands bind tubulin of trypanosomes and inhibit their growth in vitro. J Parasitol. 2002 Jun;88(3):600-4. [PubMed:12099434 ]
  5. Wampande EM, Richard McIntosh J, Lubega GW: Classical ligands interact with native and recombinant tubulin from Onchocerca volvulus with similar rank order of magnitude. Protein Expr Purif. 2007 Oct;55(2):236-45. Epub 2007 Apr 25. [PubMed:17662615 ]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Unfolded protein binding
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name:
TUBB4B
Uniprot ID:
P68371
Molecular Weight:
49830.72 Da
References
  1. Lubega GW, Geary TG, Klein RD, Prichard RK: Expression of cloned beta-tubulin genes of Haemonchus contortus in Escherichia coli: interaction of recombinant beta-tubulin with native tubulin and mebendazole. Mol Biochem Parasitol. 1993 Dec;62(2):281-92. [PubMed:8139621 ]
  2. MacDonald LM, Armson A, Thompson AR, Reynoldson JA: Characterisation of benzimidazole binding with recombinant tubulin from Giardia duodenalis, Encephalitozoon intestinalis, and Cryptosporidium parvum. Mol Biochem Parasitol. 2004 Nov;138(1):89-96. [PubMed:15500920 ]
  3. Oxberry ME, Gear TG, Prichard RK: Assessment of benzimidazole binding to individual recombinant tubulin isotypes from Haemonchus contortus. Parasitology. 2001 Jun;122(Pt 6):683-7. [PubMed:11444621 ]
  4. Ochola DO, Prichard RK, Lubega GW: Classical ligands bind tubulin of trypanosomes and inhibit their growth in vitro. J Parasitol. 2002 Jun;88(3):600-4. [PubMed:12099434 ]
  5. Wampande EM, Richard McIntosh J, Lubega GW: Classical ligands interact with native and recombinant tubulin from Onchocerca volvulus with similar rank order of magnitude. Protein Expr Purif. 2007 Oct;55(2):236-45. Epub 2007 Apr 25. [PubMed:17662615 ]
  6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Vitamin d 24-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP1A1
Uniprot ID:
P04798
Molecular Weight:
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]
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Drug created on June 13, 2005 07:24 / Updated on May 23, 2014 12:03