Mebendazole

Mebendazole Basic information
Pharmacology and mechanism of action Indications Side effects Contraindications and precautions Interactions Preparations Reference
Product Name:Mebendazole
Synonyms:(5-Benzoyl-1H-benzimidazol-2-yl)carbamicacidmethylester;(5-benzoyl-1h-benzimidazol-2-yl)-carbamicacidmethylester;(5-benzoyl-1h-benzimidazol-2-yl)-carbamicacimethylester;5-benzoyl-2-benzimidazolecarbamicacimethylester;bantenol;besantin;lomper;mbdz
CAS:31431-39-7
MF:C16H13N3O3
MW:295.29
EINECS:250-635-4
Product Categories:VERMOX;Pharmaceutical intermediates;Miscellaneous Enzyme;Amines;Aromatics;Heterocycles;Miscellaneous Natural Products;Intermediates & Fine Chemicals;Pharmaceuticals;31431-39-7
Mol File:31431-39-7.mol
Mebendazole Structure
Mebendazole Chemical Properties
Melting point 288.5°C
Boiling point 436.98°C (rough estimate)
density 1.1952 (rough estimate)
refractive index 1.6500 (estimate)
storage temp. Sealed in dry,2-8°C
solubility Practically insoluble in water, in alcohol and in methylene chloride.
form neat
pkapKa 3.43/9.93(H2O,t =25,I=0.025) (Uncertain)
color White to Pale Beige
Water Solubility 35.4mg/L(25 ºC)
Merck 14,5768
BRN 759809
BCS Class2,4
CAS DataBase Reference31431-39-7(CAS DataBase Reference)
EPA Substance Registry SystemMebendazole (31431-39-7)
Safety Information
Hazard Codes Xn
Risk Statements 22
Safety Statements 36
RIDADR UN 2811
WGK Germany 3
RTECS EY8600000
HS Code 29339900
Hazardous Substances Data31431-39-7(Hazardous Substances Data)
ToxicityLD50 orally: >80 mg/kg in sheep; >40 mg/kg in mice, rats and chickens (Van Gelder)
MSDS Information
Mebendazole Usage And Synthesis
Pharmacology and mechanism of actionMebendazole is a benzimidazole derivative with a broad spectrum of anthelminthic activity. It is highly effective against adult and larval stages of Ascaris lumbricoides, Enterobius vermicularis, Trichuris trichiura, hookworms (Ancylostoma duodenale and Necator americanus) and Capillaria philippinensis. It is also ovicidal against Ascaris lumbricoides and Trichuris trichuria [1]. With high doses, the drug has some effect against hydatid disease [2]. Recent in vitro studies have reported mebendazole to be more effective than metronidazole in killing Giardia lamblia [3,4]; however, clinical findings are inconclusive [5, 6, 7]. The mechanisms of action of benzimidazoles are similar. These drugs appear to bind to parasite tubules with subsequent inhibition of the polymerization of tubules to microtubules which is vital for the normal functioning of the parasite cells[8].
IndicationsMebendazole is the drug of choice for mixed nematode infections due to Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, Capillaria philippinensis or hookworms. The drug may be used against hydatid disease when albendazole is not available.
Side effectsDespite the widespread use of the drug, few side effects have been reported, especially in patients with heavy infections. These include transitory abdominal pain, diarrhoea and slight headache. High doses of the drug such as those used in the treatment of hydatid disease have been associated with bone marrow toxicity, alopecia, hepatitis, glomerulonephritis, fever and exfoliative dermatitis [9–12].
Contraindications and precautionsWhen high doses of mebendazole are given, regular monitoring of serum-transaminase levels and leukocyte and platelet counts must be carried out. In patients with liver impairment dosage reductions must be made.
InteractionsThe concomitant administration of phenytoin or carbamazepine has been reported to lower the plasma concentration of mebendazole [12], while cimetidine had the opposite effect[13].
Preparations• Pantelmin® (Janssen). Oral solution 20 mg/ml. Tablets 100 mg, 500 mg. • Vermox® (Janssen). Oral suspension 20 mg/ml. Tablets 100 mg, 500 mg. Several other preparations are available.
Reference1. Van den Bossche H, Rochette F, Horig C (1982). Mebendazole and related anthelminthics. Adv Pharmacol Chemother, 19, 287–296.
2. Todorov T, Vutova K, Mechkov G, Georgiev P, Petkov D, Tonchev Z, Nedelkov G (1992). Chemotherapy of human cystic echinococcosis: comparative efficacy of mebendazole and albendazole. Ann Trop Med Parasitol, 86, 59–66.
3. Cedillo-Rivera R, Munoz O (1992). In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents. J Med Microbiol, 37, 221–224.
4. Edlind TD, Hang TL, Chakraborty PR (1990). Activity of the anthelminthic benzimidazoles against Giardia lamblia in vitro. J Infect Dis, 162, 1408–1411.
5. Al-Waili D, Al-Waili B, Saloom K (1988). Therapeutic use of mebendazole in giardial infections. Trans R Soc Trop Med Hyg, 82, 438.
6. Al-Waili NSD, Hasan NU (1992). Mebendazole in giardial infections: A comparative study with metronidazole. J Infect Dis, 165, 1170–1171.
7. Gascon J, Moreno A, Valls ME, Miro JM, Corachan M (1989). Failure of mebendazole treatment in Giardia lamblia infection. Trans R Soc Trop Med Hyg, 83, 647.
8. Lacey E (1990). Mode of action of Benzimidazoles. Parasitology Today, 6, 112–115.
9. Wilson JF, Rausch RL, McMahon BJ, Schantz PM (1992). Parasitological effect of chemotherapy in alveolar hydatid disease: Review of experience with mebendazole and albendazole in Alaskan eskimos. Clin. Infect Dis, 15, 234–249.
10. Ellis M, von Sinner W, Al-hokail A, Siek JA (1992). Clinical-radiological evaluation of benzimidazoles in the management of Echinococcus granulosus cysts. Scand J Infect Dis, 24, 1–13.
11. Todorov T, Vutova K, Mechkov G, Tonchev Z, Georgiev P, Lazarova I (1992). Experience in the chemotherapy of severe, inoperable echinococcosis in man. Infection, 20, 23–24.
12. Luder PJ, Siffert B, Witassek F, Meister F, Bircher J (1986). Treatment of hydatid disease with high oral doses of mebendazole. Long-term follow-up of plasma mebendazole levels and drug interactions. Eur J Clin Pharmacol, 31, 443–448.
13. Bekhti A, Pirotte J (1987). Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts. Br J Clin Pharmacol, 24, 390–392.









DescriptionMebendazole is a broad-spectrum anthelmintic that is active against both larval and adult stages of nematodes selectively binding the β-subunit of tubulin, thereby inhibiting intestinal microtubule synthesis in the parasite (IC50 = 0.19 μM for Giardia in vitro). As a tubulin-binding agent, mebendazole also possesses antitumor properties, inducing apoptosis of various human carcinomas both in vitro and in vivo, thus preventing their growth and migration. Furthermore, mebendazole has been used to inhibit hedgehog signaling in cancer cells via suppression of the formation of the primary cilium, a microtubule-based organelle that functions as a signaling hub for hedgehog pathway activation. Additionally, mebendazole has been shown to stabilize the transcriptional activator HIF-1α and its downstream targets, abrogating oxidative neuronal death in primary neurons.
Chemical PropertiesWhite Amorphous Powder
OriginatorVermox,Ortho,US ,1975
UsesMebendazole Polymorph C is an Anthelmintic (Nematodes).
UsesFor 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.
DefinitionChEBI: A carbamate ester that is methyl 1H-benzimidazol-2-ylcarbamate substituted by a benzoyl group at position 5.
IndicationsUnlike thiabendazole, mebendazole (Vermox) does not inhibit fumarate reductase.While mebendazole binds to both mammalian and nematode tubulin, it exhibits a differential affinity for the latter, possibly explaining the selective action of the drug. The selective binding to nematode tubulin may inhibit glucose absorption, leading to glycogen consumption and ATP depletion.
Manufacturing ProcessA mixture of 5.2 parts of 4-chloro-3-nitrobenzophenone, 5 parts of ammonia, 72 parts of methanol and 13 parts of sulfolane is heated overnight at 125°C in a sealed tube. The reaction mixture is evaporated in vacuo. The semisolid residue is boiled in 100 parts of a diluted hydrochloric acid solution. After cooling, the precipitated product is filtered off and dissolved in chloroform. The chloroform phase is dried and evaporated. The residue is crystallized from toluene, yielding 4-amino-3-nitrobenzophenone; MP 141°C.
A mixture of 9.6 parts of 4-amino-3-nitrobenzophenone, 160 parts of methanol, 8 parts of concentrated hydrochloric acid and 1 part of palladiumon-charcoal catalyst 10% is hydrogenated at normal pressure and at room temperature. After the calculated amount of hydrogen is taken up, hydrogenation is stopped. The catalyst is filtered off and the solvent is evaporated. The solid residue is triturated in 2-propanol. The latter is partly evaporated and the solid product is filtered off, washed with 2-propanol and dried, yielding 3,4-diaminobenzophenone hydrochloride; MP 207°C.
7.8 parts of S-methylisothiourea sulfate are stirred in 10 parts of water in an ice bath and there are added 4.5 parts of methyl chloroformate. While keeping the temperature below 20°C, there are added dropwise, in the course of 10 minutes, 17 parts of sodium hydroxide solution 25% (pH 8±), followed by the addition of 5.6 parts of acetic acid (pH 5). To this mixture is added at 20°C a suspension of 7 parts of 3,4-diaminobenzophenone hydrochloride in 100 parts of water, followed by the addition of 2.3 parts of sodium acetate.
The whole is slowly heated to 85°C and stirred at this temperature for 45 minutes. The reaction mixture is cooled and the precipitated product is filtered off. It is washed successively with water and ethanol, dried and crystallized from a mixture of acetic acid and methanol, yielding methyl N-[5(6)-benzoyl2-benzimidazolyl]carbamate; MP 288.5°C.
Brand nameVermox (McNeil).
Therapeutic FunctionAnthelmintic
General DescriptionWhite to slightly yellow powder. Pleasant taste. Practically water insoluble.
Air & Water ReactionsInsoluble in water.
Reactivity ProfileMebendazole is a carbamate ester-amine. Amines behave as chemical bases. Carbamates are chemically similar to, but more reactive than amides. Like amides they form polymers such as polyurethane resins. Carbamates are incompatible with strong acids and bases, and especially incompatible with strong reducing agents such as hydrides. Flammable gaseous hydrogen is produced by the combination of active metals or nitrides with carbamates. Strongly oxidizing acids, peroxides, and hydroperoxides are incompatible with carbamates.
Fire HazardFlash point data for Mebendazole are not available; however, Mebendazole is probably combustible.
Pharmaceutical ApplicationsA benzimidazole carbamic acid methyl ester available for oral administration. It is insoluble in water and stable at room temperature.
Mechanism of actionMebendazole is given orally; it is poorly soluble, and very little is absorbed from the intestinal tract. About 5 to 10%, principally the decarboxylated derivatives, is recovered in the urine; most of the orally administered drug is found in the feces within 24 hours.
PharmacokineticsOral absorption is poor. Plasma concentrations achieved after oral administration of 100 mg every 12 h for three consecutive days do not exceed 0.03 mg/L. All metabolites are inactive. Most of the dose, as unchanged drug or a primary metabolite, is retained in the intestinal tract and passed in the feces, with the remainder, approximately 2% of the dose, excreted in the urine.
Clinical UseMethyl 5-benzoyl-2-benzimidazolecarbamate (Vermox) isa broad-spectrum anthelmintic that is effective against variousnematode infestations, including whipworm, pinworm,roundworm, and hookworm. Mebendazole irreversiblyblocks glucose uptake in susceptible helminths, thereby depletingglycogen stored in the parasite. It apparently does notaffect glucose metabolism in the host. It also inhibits cell divisionin nematodes.
Mebendazole is poorly absorbed by the oral route.Adverse reactions are uncommon and usually consist of abdominaldiscomfort. It is teratogenic in laboratory animalsand, therefore, should not be given during pregnancy.
Clinical UseMebendazole is used primarily for the treatment of A. lumbricoides, T. trichiura, E. vermicularis, and hookworm infections, in which it produces high cure rates. It is an alternative agent for the treatment of trichinosis and visceral larva migrans. Owing to its broad-spectrum anthelmintic effect, mixed infections (ascariasis, hookworm infestation, or enterobiasis in association with trichuriasis) frequently respond to therapy. High doses have been used to treat hydatid disease, but albendazole is now thought to be superior.
Clinical UseIntestinal nematode infections
Trichinosis (larval stage)
Side effectsAbdominal discomfort and diarrhea may occur when the worm load is heavy. Its use is contraindicated during pregnancy.
Side effectsDiarrhea and gastrointestinal discomfort may occur, but adverse reactions are generally mild. Woman of childbearing age should be informed of a potential risk to the fetus if treated during pregnancy, particularly during the first trimester.
Safety ProfileModerately toxic by ingestion and intraperitoneal routes. Human mutation data reported. An experimental teratogen. Experimental reproductive effects. When heated to decomposition it emits toxic fumes of NOx. See also CARBAMATES.
SynthesisMebendazole, methyl-[5-(benzoyl)-1H-benzoimidazol-2-yl]carbamate (38.1.5), is a derivative of benzoimidazole, which is made by reacting 3,4-diaminobenzophenone (38.1.3) with N-methoxycarbonyl-S-methylthiourea (38.1.4).
Synthesis_31431-39-7_1
The necessary reagents are made in the following manner. Nitration of 4-chlorobenzophenone with nitric acid at a temperature lower than 5°C gives 4-chloro-3-nitrobenzophenone (38.1.1), in which the chlorine atom is replaced with an amino group by heating it to 125°C in a solution of ammonia in methanol to make 4-amino-3-nitrobenzophenone (38.1.2). Reducing the nitro groups in this compound with hydrogen using a palladium on carbon catalyst gives 3,4-diaminobenzophenone (38.1.3).
Synthesis_31431-39-7_2
The second reagent, N-methoxycarbonyl-S-methylthiourea (38.1.4), is made by reacting methyl chloroformate with S-methylthiourea.
Synthesis_31431-39-7_3
references[1]. seo bs, cho sy, kang sy, et al. anthelmintic efficacy of methyl-5-benzoylbenzimidazole-2-carbamate(mebendazole) against multiple helminthic infections. kisaengchunghak chapchi. 1977 jun;15(1):11-16.
[2]. morgan um, reynoldson ja, thompson rc. activities of several benzimidazoles and tubulin inhibitors against giardia spp. in vitro. antimicrob agents chemother. 1993 feb;37(2):328-31.
[3]. doudican n, rodriguez a, osman i, et al. mebendazole induces apoptosis via bcl-2 inactivation in chemoresistant melanoma cells. mol cancer res. 2008 aug;6(8):1308-15.
[4]. mukhopadhyay t, sasaki j, ramesh r, et al. mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo. clin cancer res. 2002 sep;8(9):2963-9.
[5]. sasaki j, ramesh r, chada s, et al. the anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells. mol cancer ther. 2002 nov;1(13):1201-9.
[6]. larsen ar, bai ry, chung jh, et al. repurposing the antihelmintic mebendazole as a hedgehog inhibitor. mol cancer ther. 2015 jan;14(1):3-13.
[7]. aleyasin h, karuppagounder ss, kumar a, et al. antihelminthic benzimidazoles are novel hif activators that prevent oxidative neuronal death via binding to tubulin. antioxid redox signal. 2015 jan 10;22(2):121-34.
Methylparaben Albendazole Benzoyl peroxide Oxibendazole Methyl Methyl phenylacetate Benzimidazole Bensulfuron methyl Midazolam 1,3-Diphenylguanidine Benzophenone Kresoxim-methyl Methyl benzoate Methyl acrylate Benzoyl chloride Fenbendazole Methyl bromide Oxybenzone Mebendazol

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