Miconazole

Chemical Properties

White or almost white powder.

Originator

Daktarin,Janssen,Italy,1974

Uses

Miconazole, is used as an antifungal inhibitor of aromatase. Miconazole has been shown to promote remyelination of neurons in chronic progressive multiple sclerosis mouse models. Miconazole is mainly used externally for the treatment of athlete's foot, ringworm, and jock itch. Internal application is used for oral or vaginal thrush (yeast infection). The oral gel may also be used for the lip disorder angular cheilitis. It is also used in photography.

Uses

Miconazole is an antifungal agent of the imidazole type. It is used in topical and vaginal preparations to prevent growth of dermatophytes, yeast, and molds.

Uses

Antifungal;Sterol 14-demethylase inhibitor.
Miconazole (Monistat-Derm, Micatin, etc.) is a synthetic imidazole antifungal compound that acts by altering cell membrane permeability. It is effective against most dermatophyte species, P. orbiculare, and C. albicans.

Definition

ChEBI: 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]imidazole is a member of the class of imidazoles that is 1-(2,4-dichlorophenyl)-2-(imidazol-1-yl)ethanol in which the hydroxyl hydrogen is replaced by a 2,4-dichlorobenzyl group. It is an ether, a member of imidazoles and a dichlorobenzene.

Indications

Miconazole (Monistat) is a broad-spectrum imidazole antifungal agent used in the topical treatment of cutaneous dermatophyte infections and mucous membrane Candida infections, such as vaginitis. Minimal absorption occurs from skin or mucous membrane surfaces. Local irritation to skin and mucous membranes can occur with topical use; headaches, urticaria, and abdominal cramping have been reported with treatment for vaginitis.

Manufacturing Process

Imidazole is reacted with ω-bromo-2,4-dichloroacetophenone and that product reduced with sodium borohydride.
A suspension of 10.3 parts of the α-(2,4-dichlorophenyl)imidazole-1-ethanol thus obtained and 2.1 parts of sodium hydride in 50 parts of dry tetrahydrofuran is stirred and refluxed for 2 hours. After this reaction time, the evolution of hydrogen is ceased. Then there are added successively 60 parts dimethylformamide and 8 parts of 2,4-dichlorobenzyl chloride and stirring and refluxing are continued for another 2 hours. The tetrahydrofuran is removed at atmospheric pressure. The dimethylformamide solution is poured onto water.
The product, 1-[2,4-dichloro-β-(2,4 -dichlorobenzyloxy)phenethyl]imidazole, is extracted with benzene. The extract is washed with water, dried, filtered and evaporated in vacuo. From the residual oily free base, the nitrate salt is prepared in the usual manner in 2-propanol by treatment with concentrated nitric acid, yielding, after recrystallization of the crude solid salt from a mixture of 2-propanol, methanol and diisopropyl ether, 1-[2,4-dichloro-β- dichlorobenzyloxy)phenethyl]imidazole nitrate; melting point 170.5°C.

brand name

M-Zole (Actavis); Monistat (Ortho-McNeil); Monistat (Personal Products); Monistat (Johnson & Johnson).

Therapeutic Function

Antifungal

Clinical Use

Antifungal agent

Synthesis

Miconazole, 1-[2,4-dichloro-|?-[(2,4-dichlorobenzyl)oxy]phenethyl]-imidazole (35.2.7), like ketoconazol, is synthesized from 2,4-dichlorophenacylbromide, which is reacted with imidazole to make 1-(2,4-dichlorobenzoylmethyl)-imidazole[2,4-dichloro-|?-(1-imidazolyl)-acetophenone] (35.2.5). Reducing the carbonyl group in this molecule with sodium borohydride gives 1-(2,4-dichlorophenyl)-3-(1-imidazolyl)-ethanol (35.2.6), and the hydroxyl group is alkylated by 2,4-dichlorobenzylbromide using a powerful base such as sodium hydride to make miconazole (35.2.7).

Veterinary Drugs and Treatments

Miconazole is a broad spectrum imidazole antifungal agent with some antibacterial activity. Miconazole will penetrate the intact corneal epithelium. Topical miconazole therapy has been a favorite first choice agent for treatment of fungal keratitis in the horse by veterinary ophthalmologists for several years. Miconazole may be delivered by subconjunctival route, but with some local irritation, and topical use is the most commonly employed treatment method.

Veterinary Drugs and Treatments

Topical miconazole has activity against dermatophytes and yeasts; miconazole shampoos can be effective treatment for Malassezia dermatitis. Patients with severe, generalized infections may require systemic therapy. Lotions, sprays and creams are generally used for localized lesions associated with Malassezia or dermatophytes. See otic section for information on application for Malassezia otitis externa.
Topical miconazole products are generally ineffective (or minimally effective) when used alone for dermatophytosis; adjunctive systemic treatment is usually required.
Miconazole’s actions are a result of altering permeability of fungal cellular membranes and interfering with peroxisomal and mitochondrial enzymes, leading to intracellular necrosis. Miconazole products are fungicidal with repeated application.

Drug interactions

Potentially hazardous interactions with other drugs
Anticoagulants: effect of coumarins enhanced. Antidepressants: avoid concomitant use with reboxetine.
Antidiabetics: enhances hypoglycaemic effect of gliclazide and glipizide; concentration of sulphonylureas increased.
Antiepileptics: effect of fosphenytoin and phenytoin enhanced; possibly increased carbamazepine concentration.
Antihistamines: avoid with mizolastine, risk of ventricular arrhythmias.
Antimalarials: avoid with piperaquine with artenimol and artemether with lumefantrine
. Antipsychotics: increased risk of ventricular arrhythmias with pimozide - avoid; possibly increased concentration of quetiapine - avoid.
Antivirals: concentration of saquinavir possibly increased.
Ciclosporin: possibly increased ciclosporin concentration.
Ergot alkaloids: increased risk of ergotism with ergotamine and methysergide - avoid.
Sirolimus: concentration increased by miconazole.
Statins: possibly increased risk of myopathy with atorvastatin and simvastatin - avoid with simvastatin.
Tacrolimus: possibly increased tacrolimus concentration

Metabolism

Miconazole is metabolised in the liver to inactive metabolites; 10-20% of an oral dose is excreted in the urine as metabolites. About 50% of an oral dose may be excreted mainly unchanged in the faeces