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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
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 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
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
    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 solubility3.87e-02 g/lALOGPS
    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 area84.08ChemAxon
    rotatable bond count4ChemAxon
    refractivity81.5ChemAxon
    polarizability31.1ChemAxon
    number of rings3ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis ReferenceNot Available
    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.

    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

    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

    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

    Comments
    Drug created on June 13, 2005 07:24 / Updated on January 15, 2014 09:36