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Identification
Name Mebendazole
Accession Number DB00643 (APRD01086)
Type small molecule
Groups approved
Description

A benzimidazole that acts by interfering with carbohydrate metabolism and inhibiting polymerization of microtubules. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Bantenol
  • Besantin
  • Equivurm Plus
  • Lomper
  • MBDZ
  • Mebendazole (JAN/USP)
  • MEBENDAZOLE, 99%
  • Mebendazole(USAN)
  • Mebenoazole
  • Mebenvet
  • Mebex
  • Mebutar
  • Noverme
  • Ovitelmin
  • Pantelmin
  • Telmin
  • Vermicidin
  • Vermirax
  • Vermox
  • Vermox (TN)
  • Verpanyl
Brand name mixtures
  • Bot-Plus Syringe Formula Equine Wormer (Mebendazole + Trichlorfon)
  • Equiverm B Pst (Mebendazole + Trichlorfon)
  • Telmin B Syringe Formula (Mebendazole + Trichlorfon)
Categories
  • Antinematodal Agents
  • Tubulin Modulators
CAS number 31431-39-7
Weight Average: 295.2927
Monoisotopic: 295.095691297
Chemical Formula C16H13N3O3
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzimidazoles
  • Benzoyl Derivatives
Substructures
  • Carbamates and Derivatives
  • Benzimidazoles
  • Ethers
  • Benzene and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Benzoyl Derivatives
  • Cyanamides
  • Ketones
Pharmacology
Indication For 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.
Pharmacodynamics Mebendazole 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 action Mebendazole 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.
Absorption Poorly absorbed (approximately 5 to 10%) from gastrointestinal tract. Fatty food increases absorption.
Volume of distribution Not Available
Protein binding 90-95%
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.
Route of elimination In man, approximately 2% of administered mebendazole is excreted in urine and the remainder in the feces as unchanged drug or a primary metabolite.
Half life 2.5 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).
Clearance Not Available
Toxicity Acute 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
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Teva pharmaceuticals usa
  • Mcneil pediatrics
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Mebendazole 100 mg Chew Tabs 16.42 USD tab
Mebendazole 100 mg tablet chew 5.32 USD tablet
Mebendazole powder 5.03 USD g
Vermox 100 mg Chewable Tablet 4.14 USD tablet
Patents Not Available
Properties
State solid
Melting point 288.5 oC
Experimental Properties
Property Value Source
water solubility 71.3 mg/L PhysProp
logP 2.8 PhysProp
logS -3.88 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 3.87e-02 g/l ALOGPS
logP 2.95 ALOGPS
logP 3.26 ChemAxon Molconvert
logS -3.88 ALOGPS
pKa 13.92 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 84.08 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 81.50 ChemAxon Molconvert
polarizability 31.10 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Link
External Links
Resource Link
KEGG Drug D00368 Link_out
PubChem Compound 4030 Link_out
PubChem Substance 46508807 Link_out
ChemSpider 3890 Link_out
ChEBI 6704 Link_out
ChEMBL 6704 Link_out
Therapeutic Targets Database DAP000950 Link_out
PharmGKB PA450333 Link_out
Drug Product Database 556734 Link_out
RxList http://www.rxlist.com/cgi/generic3/mebend.htm Link_out
Drugs.com http://www.drugs.com/cdi/mebendazole.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mebendazole Link_out
ATC Codes
  • P02CA01
AHFS Codes
  • 08:08.00
PDB Entries Not Available
FDA label Not Available
MSDS show (72.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Lipid rich meals may improve absorption.
  • Take with food.
Targets

1. Tubulin alpha-3 chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: Q71U36 Link_out
Gene: TUBA1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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-2C chain

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P68371 Link_out
Gene: TUBB2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inducer

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

UniProt ID: P04798 Link_out
Gene: CYP1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 April 19, 2011 15:05

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.