Butenafine: Difference between revisions

{{short description|Chemical compound}}

{{cs1 config|mode=cs1|name-list-style=vanc|display-authors=6}}

| verifiedrevid = 459987694

| image = Butenafine.svg

| width =

| tradename = Mentax, Lotrimin Ultra

| pregnancy_US = C

| pregnancy_US_comment = <ref>{{cite web|title=Mentax (butenafine hydrochloride) Cream. Human Prescription Drug Label|url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=167ecefd-4553-41b8-8160-81a48dbca076|website=dailymed.nlm.nih.gov| author =Mylan Pharmaceuticals Inc. | publisher = National Institutes of Health, U.S. National Library of Medicine, Health & Human Services |access-date=24 August 2016}}</ref>

| legal_status = OTC (Lotrimin Ultra), Rx-only&nbsp;(Mentax)

| routes_of_administration = [[Topical medication|Topical]] ([[Cream (pharmaceutical)|cream]])

| bioavailability =

| protein_bound =

| elimination_half-life = 35–100 hours

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| synonyms =

| C=23 | H=27 | N=1

| SMILES = N(C)(Cc1ccc(cc1)C(C)(C)C)Cc3c2ccccc2ccc3

'''Butenafine''', sold under the brand names '''Lotrimin Ultra''', '''Mentax''', and '''Butop''' (In [[India]] only), is a [[synthetic compound|synthetic]] [[benzylamine]] derived [[antifungal medication|antifungal drug]].

It is structurally related to the [[allylamine]] antifungals [[terbinafine]] & [[naftifine]].

==Medical uses==

Butenafine is indicated for the topical treatment of tinea (pityriasis) versicolor due to ''[[Malassezia|Malassezia furfur]]'', as well as [[athlete's foot]] (''Tinea pedis''), [[ringworm]] (''Tinea corporis'') and [[jock itch]] (''Tinea cruris'') due to ''[[Epidermophyton floccosum]]'', ''[[Trichophyton interdigitale|Trichophyton mentagrophytes]]'', ''[[Trichophyton rubrum]]'', and ''[[Trichophyton tonsurans]]''.

It also displays superior activity against ''[[Candida albicans]]'' than terbinafine and [[naftifine]]. Butenafine demonstrates low minimum inhibitory concentrations against ''[[Cryptococcus (fungus)|Cryptococcus]]'' and ''[[Aspergillus]]''.

There is some evidence that it is effective against dermatophyte infections of the toenails, but needs to be applied daily for prolonged periods (at least one year).<ref>{{cite journal | vauthors = Crawford F, Hollis S | title = Topical treatments for fungal infections of the skin and nails of the foot | journal = The Cochrane Database of Systematic Reviews | volume = 2007 | issue = 3 | pages = CD001434 | date = July 2007 | pmid = 17636672 | pmc = 7073424 | doi = 10.1002/14651858.CD001434.pub2 }}</ref>

===Available forms===

==Pharmacology==

Like the allylamine antifungals (e.g [[terbinafine]]), butenafine works by inhibiting the synthesis of [[ergosterol]] by binding to and inhibiting [[squalene epoxidase]], an enzyme in the pathway used for creation of the sterols needed in fungal cell membranes. Lacking ergosterol, the cell membranes increase in permeability, allowing their contents to leak out. Furthermore, inhibition of squalene epoxidase leads to a toxic buildup of squalene. This double action of butenafine (increased membrane permeability and toxic buildup of squalene) makes butenafine fungicidal rather than merely fungistatic.

In addition to being an antifungal, butenafine is an anti inflammatory. Because fungal skin infections are often accompanied by significant inflammation, this is a desirable property. The fact that butenafine has intrinsic anti inflammatory properties is also desirable since it is not necessary to add topical [[glucocorticoid]]s, which often come with undesired side effects.

==Chemistry==

Butenafine [[hydrochloride]] is an odorless white crystalline powder that is freely soluble in [[methanol]], [[ethanol]], and [[chloroform]], yet is only slightly soluble in water.

==Synthesis==

:[[File:Butenafine synthesis.svg|500px]]

[[Reductive amination]] of [[Naphthalene#Naphthalene_derivatives|1-naphthaldehyde]] (1) with [[methylamine]] (2) gives the intermediate secondary [[amine]] (3). [[Alkylation]] of this with p-[[tert-butyl]] [[benzyl bromide]] (4) yields the tertiary amine butenafine.<ref>{{cite patent |country=US |number=5021458 |inventor=Maeda T, Yamamoto T, Takase M, Sasaki K, Arika T, Yokoo M, Hashimoto R, Amemiya K, Koshikawa S |title=Amine derivatives and fungicides containing the same |status=patent |gdate=1991-06-04 |fdate=1988-12-07 |assign1=Kaken Pharmaceutical Co Ltd}}</ref><ref>{{cite journal | vauthors = Maeda T, Takase M, Ishibashi A, Yamamoto T, Sasaki K, Arika T, Yokoo M, Amemiya K | title = [Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent] | language = JA | journal = Yakugaku Zasshi | volume = 111 | issue = 2 | pages = 126–137 | date = February 1991 | pmid = 2056447 | doi = 10.1248/yakushi1947.111.2_126 | doi-access = free }}</ref><ref>{{cite web |url=https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-02-0157 |title=Butenafine | work = Pharmaceutical Substances |publisher=Thieme |access-date=2024-07-04}}</ref>

== References ==

{{Reflist}}

{{Antifungals}}

[[Category:Tertiary amines]]

[[Category:Antifungals]]

[[Category:1-Naphthyl compounds]]

[[Category:Tert-butyl compounds]]