Naftifine

Absorption

Following single topical applications of 3H-labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed.

Originator

Naftifine,Sandoz (Novartis)

The Uses of Naftifine

(E)-Naftifine is an intermediate in synthesizing Naftifine N-Oxide (N213110), which is an impurity or metabolite of Naftifine Hydrochloride (N213100), an allylamine antifungal agent.

The Uses of Naftifine

Naftifine (Naftin) is a synthetic allylamine derivative topical antifungal agent that works by blocking squalene 2,3-epoxidase, resulting in increased cell membrane permeability and cell death. It is structurally and pharmacologically related to terbinafine. It also has some antiinflammatory properties that may be due to its ability to alter chemotaxis by polymorphonucleocytes. It is most effective against dermatophytes, moderately active against molds, and less active against yeasts, including C. albicans.

The Uses of Naftifine

Naftifine is only permitted to be used externally and only superficially as a drug with a broad spectrum of action against dermatophytes and candida infections. According to the initial data, it exceeds the activity of econazole. Moreover, it does not have a locally irritating effect. It is believed that the fungicide activity of this drug is based on its ability to inhibit the fungal enzyme squalene epoxidase, thus lowering the concentration of ergosterol. The corresponding enzyme in mammals is inhibited significantly less. Synonyms of this drug are exoderil, naftin, and others.

Background

Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative for the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum.

Indications

For the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum.

Definition

ChEBI: A tertiary amine in which the nitrogen is substituted by methyl, alpha-naphthylmethyl, and (1E)-cinnamyl groups. It is used (usually as its hydrochloride salt) for the treatment of fungal skin infections.

Indications

Naftifine (Naftin) is a synthetic allylamine derivative topical antifungal agent that works by blocking squalene 2,3-epoxidase, resulting in increased cell membrane permeability and cell death. It is structurally and pharmacologically related to terbinafine. It also has some antiinflammatory properties that may be due to its ability to alter chemotaxis by polymorphonucleocytes. It is most effective against dermatophytes, moderately active against molds, and less active against yeasts, including C. albicans.

Manufacturing Process

To a mixture of 1.42 g of methyl-(1-naphthylmethyl)amine hydrochloride, 2.89 g of sodium carbonate and 10 ml of dimethylformamide is added, at room temperature, 1.25 g of cinnamyl chloride, dropwise. After 18 hours stirring, at room temperature, the mixture is filtered and the filtrate is evaporated in vacuo. The residue is dissolved in toluene and, after drying over sodium sulphate, evaporated to obtain the trans-N-(cinnamylmethyl)-Nmethyl-(1-naphthylmethyl)amine compound, boiling point 162-167°C/0.015 Torr.
The free base may be converted, with isopropanolic hydrogen chloride solution, into the hydrochloride form, melting point 177°C (from propanol).

brand name

Naftin (Merz).

Therapeutic Function

Antifungal

Synthesis Reference(s)

Journal of Medicinal Chemistry, 29, p. 112, 1986 DOI: 10.1021/jm00151a019
Tetrahedron Letters, 25, p. 2535, 1984 DOI: 10.1016/S0040-4039(01)81224-7

Antimicrobial activity

Naftifine is fungicidal against dermatophytes such as Epidermophyton floccosum, Trichophyton and Microsporum species. Against pathogenic yeasts such as Candida species and moulds, it shows only an intermediate fungistatic activity in vitro.

Pharmaceutical Applications

A topical antifungal used as a 1% cream for the treatment of dermatophytoses, including tinea pedis, tinea corporis and tinea cruris.

Pharmacokinetics

Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative. The following in vitro data are available, but their clinical significance is unknown. Naftifine has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis, Microsporum audouini, and Microsporum gypseum; and fungistatic activity against Candida species including Candida albicans. However it is only used to treat the organisms listed in the indications.

Pharmacokinetics

Naftifine penetrates well into the stratum corneum of the skin; 2 – 4 % of the topically administered dose were absorbed after administration of a 1 % gel preperation. After occlusion, an absorption of 6% of the administered dose was observed.

Clinical Use

Naftifine was the first allyl amine to be discovered and marketed. It is subject to extensive first-pass metabolism to be orally active and, consequently, is only available in topical preparations. The widest use of naftifine is against various tinea infections of the skin.

Side Effects

Naftifine is well tolerated although rare cases of local skin irritations and contact dermatitis have been found, which might also be due the galenic formulation.

Synthesis

Naftifine, (E)-N-methyl-N-(3-phenyl-2-propenyl)-1-naphthalinmethanamine (35.3.1), is synthesized by alkylating N-methyl-(1-naphthylmethyl)-amine with cinnamyl chloride in the presence of sodium carbonate.

Metabolism

Not Available