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Identification
NameMebendazole
Accession NumberDB00643  (APRD01086)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
SynonymLanguageCode
(5-benzoyl-1H-benzimidazol-2-yl)-carbamic acid methyl esterNot AvailableNot Available
MBDZNot AvailableNot Available
MebendazolGermanINN
MebendazolSpanishINN
MébendazoleFrenchINN
MebendazolumLatinINN
VermoxNot AvailableNot Available
SaltsNot Available
Brand names
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 mixtures
Brand NameIngredients
Equiverm BMebendazole and Trichlorfon
Mebex PlusMebendazole and Pyrantel
Telmin B Syringe FormulaMebendazole and Trichlorfon
Categories
CAS number31431-39-7
WeightAverage: 295.2927
Monoisotopic: 295.095691297
Chemical FormulaC16H13N3O3
InChI KeyOPXLLQIJSORQAM-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzophenones
Direct parentBenzophenones
Alternative parentsAcetophenones; Benzimidazoles; Benzoyl Derivatives; Aminoimidazoles; Carbamic Acids and Derivatives; Ketones; Ethers; Enolates; Polyamines
Substituentsacetophenone; benzimidazole; benzoyl; aminoimidazole; imidazole; azole; ketone; carbamic acid derivative; polyamine; ether; enolate; carbonyl group; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.9932
Blood Brain Barrier + 0.9261
Caco-2 permeable + 0.7261
P-glycoprotein substrate Non-substrate 0.6073
P-glycoprotein inhibitor I Inhibitor 0.5844
P-glycoprotein inhibitor II Inhibitor 0.7534
Renal organic cation transporter Non-inhibitor 0.8464
CYP450 2C9 substrate Non-substrate 0.749
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Non-substrate 0.6532
CYP450 1A2 substrate Inhibitor 0.9107
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8308
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6779
Ames test AMES toxic 0.7212
Carcinogenicity Non-carcinogens 0.9102
Biodegradation Not ready biodegradable 0.994
Rat acute toxicity 2.5855 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9515
hERG inhibition (predictor II) Non-inhibitor 0.8028
Pharmacoeconomics
Manufacturers
  • Teva pharmaceuticals usa
  • Mcneil pediatrics
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Mebendazole 100 mg Chew Tabs16.42USDtab
Mebendazole 100 mg tablet chew5.32USDtablet
Mebendazole powder5.03USDg
Vermox 100 mg Chewable Tablet4.14USDtablet
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 Solubility0.0387ALOGPS
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

U.S. Patent 3,657,267.

General Reference
  1. Link
External Links
ResourceLink
KEGG DrugD00368
PubChem Compound4030
PubChem Substance46508807
ChemSpider3890
ChEBI6704
ChEMBLCHEMBL685
Therapeutic Targets DatabaseDAP000950
PharmGKBPA164776669
Drug Product Database556734
RxListhttp://www.rxlist.com/cgi/generic3/mebend.htm
Drugs.comhttp://www.drugs.com/cdi/mebendazole.html
WikipediaMebendazole
ATC CodesP02CA01
AHFS Codes
  • 08:08.00
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(72.8 KB)
Interactions
Drug Interactions
Drug
EthotoinThe hydantoin decreases the efficiency of mebendazole
FosphenytoinThe hydantoin decreases the efficiency of mebendazole
MephenytoinThe hydantoin decreases the efficiency of mebendazole
PhenytoinThe hydantoin decreases the efficiency of mebendazole
Food Interactions
  • Lipid rich meals may improve absorption.
  • Take with food.

Targets

1. Tubulin alpha-1A chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin alpha-1A chain Q71U36 Details

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
  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
  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
  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
  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
  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

2. Tubulin beta-4B chain

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tubulin beta-4B chain P68371 Details

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
  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
  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
  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
  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
  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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

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. Epub 2009 Nov 24. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

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Drug created on June 13, 2005 07:24 / Updated on May 23, 2014 12:03