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Details

Stereochemistry ACHIRAL
Molecular Formula C23H27N.ClH
Molecular Weight 353.928
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BUTENAFINE HYDROCHLORIDE

SMILES

Cl.CN(CC1=CC=C(C=C1)C(C)(C)C)CC2=CC=CC3=CC=CC=C23

InChI

InChIKey=LJBSAUIFGPSHCN-UHFFFAOYSA-N
InChI=1S/C23H27N.ClH/c1-23(2,3)21-14-12-18(13-15-21)16-24(4)17-20-10-7-9-19-8-5-6-11-22(19)20;/h5-15H,16-17H2,1-4H3;1H

HIDE SMILES / InChI
Butenafine is a synthetic antifungal agent that is structurally and pharmacologically related to allylamine antifungals. The exact mechanism of action has not been established, but it is suggested that butenafine's antifungal activity is exerted through the alteration of cellular membranes, which results in increased membrane permeability, and growth inhibition. Butenafine is mainly active against dermatophytes and has superior fungicidal activity against this group of fungi when compared to that of terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. It is also active against Candida albicans and this activity is superior to that of terbinafine and naftifine. Butenafine also generates low MICs for Cryptococcus neoformans and Aspergillus spp. as well. Butenafine hydrochloride is marketed under the trade names Mentax, Butop (India) and is the active ingredient in Lotrimin Ultra. MENTAX Cream, 1%, is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur (formerly Pityrosporum orbiculare). Although the mechanism of action has not been fully established, it has been suggested that butenafine, like allylamines, interferes with sterol biosynthesis (especially ergosterol) by inhibiting squalene monooxygenase, an enzyme responsible for converting squalene to 2,3-oxydo squalene. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Blockage of squalene monooxygenase also leads to a subsequent accumulation of squalene. When a high concentration of squalene is reached, it is thought to have an effect of directly kill fungal cells. Butenafine cream 1% is indicated in treatment of tinea pedis, tinea corporis and tinea cruris. In tinea pedis it is recommended twice daily for 7 days or once daily for 4 weeks. In tinea cruris and tinea corporis it is recommended once daily for two weeks.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MENTAX

Approved Use

MENTAX-TC Cream, 1%, is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur (formerly Pityrosporum orbiculare).

Launch Date

1996
Primary
Butenafine

Approved Use

OTC labeling: Topical treatment of tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm)

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.4 ng/mL
6 g 1 times / day multiple, topical
dose: 6 g
route of administration: Topical
experiment type: MULTIPLE
co-administered:
BUTENAFINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
5 ng/mL
20 g 1 times / day multiple, topical
dose: 20 g
route of administration: Topical
experiment type: MULTIPLE
co-administered:
BUTENAFINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
23.9 ng × h/mL
6 g 1 times / day multiple, topical
dose: 6 g
route of administration: Topical
experiment type: MULTIPLE
co-administered:
BUTENAFINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
87.8 ng × h/mL
20 g 1 times / day multiple, topical
dose: 20 g
route of administration: Topical
experiment type: MULTIPLE
co-administered:
BUTENAFINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
35 h
20 g 1 times / day multiple, topical
dose: 20 g
route of administration: Topical
experiment type: MULTIPLE
co-administered:
BUTENAFINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 % 1 times / day multiple, topical
Recommended
Dose: 1 %, 1 times / day
Route: topical
Route: multiple
Dose: 1 %, 1 times / day
Sources: Page: CL2001-01
unhealthy, 2-12
n = 100
Health Status: unhealthy
Condition: Tinea corporis
Age Group: 2-12
Sex: M+F
Population Size: 100
Sources: Page: CL2001-01
PubMed

PubMed

TitleDatePubMed
[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].
1991 Feb
Two mechanisms of butenafine action in Candida albicans.
1993 Apr
Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment.
1993 Jul 23
Butenafine, a fungicidal benzylamine derivative, used once daily for the treatment of interdigital tinea pedis.
1998 Jun
Butenafine.
1998 Mar
Butenafine hydrochloride: for the treatment of interdigital tinea pedis.
2000 Mar
Butenafine hydrochloride (Mentax) cream for the treatment of hyperkeratotic type tinea pedis and its transfer into the horny layer, with or without concomitant application of 20% urea ointment (Keratinamin).
2001
Comparison of in vitro antifungal activities of topical antimycotics launched in 1990s in Japan.
2001 Aug
KP-103, a novel triazole derivative, is effective in preventing relapse and successfully treating experimental interdigital tinea pedis and tinea corporis in guinea pigs.
2002
Six novel antimycotics.
2002
A Japanese case of tinea corporis caused by Arthroderma benhamiae.
2002 Apr
Butenafine: an update of its use in superficial mycoses.
2002 Sep
Evaluation of in vitro activity of ciclopirox olamine, butenafine HCl and econazole nitrate against dermatophytes, yeasts and bacteria.
2003 Sep
In vitro antifungal activity of ZJ-522, a new triazole restructured from fluconazole and butenafine, against clinically important fungi in comparison with fluconazole and butenafine.
2005 Aug
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
An unprecedented rearrangement in collision-induced mass spectrometric fragmentation of protonated benzylamines.
2006 Sep
Fungal toenail infections.
2008 Dec 15
Butenafine and superficial mycoses: current status.
2008 Jul
Are placebo-controlled trials of creams for athlete's foot still justified?
2008 Sep
In vitro antifungal activities of luliconazole, a new topical imidazole.
2009
Update on terbinafine with a focus on dermatophytoses.
2009 Apr 21
Simultaneous HPLC determination of butenafine hydrochloride and betamethasone in a cream formulation.
2009 Sep
[Activity of butenafine against ocular pathogenic filamentous fungi in vitro].
2010 Jan
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Sample Use Guides

Patients with tinea (pityriasis) versicolor should apply MENTAX-TC Cream, 1% (Butenafine), once daily for seven days. Sufficient MENTAX-TC Cream, 1%, should be applied to cover affected areas and extending 4 inches (10.2 cm) onto normal skin immediately surrounding the affected area.
Route of Administration: Topical
Butenafine HCl shows minimum inhibitory concentrations ranging from 0.03–1.0 ug/mL against 30 isolates representing different dermatophyte species.
Name Type Language
BUTENAFINE HYDROCHLORIDE
JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
BUTENAFINE HYDROCHLORIDE [VANDF]
Common Name English
BUTENAFINE HYDROCHLORIDE [MI]
Common Name English
BUTENAFINE HCL
Common Name English
BUTENAFINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
VOLLEY
Brand Name English
BUTENAFINE HYDROCHLORIDE [MART.]
Common Name English
BUTENAFINE HYDROCHLORIDE [JAN]
Common Name English
MENTAX
Brand Name English
1-NAPHTHALENEMETHANAMINE, N-((4-(1,1-DIMETHYLETHYL)PHENYL)METHYL)-N-METHYL-, HYDROCHLORIDE
Systematic Name English
KP-363
Code English
Butenafine hydrochloride [WHO-DD]
Common Name English
N-(P-TERT-BUTYLBENZYL)-N-METHYL-1-NAPHTHALENEMETHYLAMINE HYDROCHLORIDE
Common Name English
BUTENAFINE HYDROCHLORIDE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C514
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Code System Code Type Description
EVMPD
SUB00914MIG
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PRIMARY
DRUG BANK
DBSALT000245
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PRIMARY
FDA UNII
R8XA2029ZI
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PRIMARY
EPA CompTox
DTXSID2048589
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PRIMARY
USAN
II-94
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PRIMARY
CHEBI
31325
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PRIMARY
PUBCHEM
443867
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PRIMARY
NCI_THESAURUS
C47426
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PRIMARY
SMS_ID
100000084840
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PRIMARY
ChEMBL
CHEMBL990
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PRIMARY
CAS
101827-46-7
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PRIMARY
DAILYMED
R8XA2029ZI
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PRIMARY
MERCK INDEX
m2791
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PRIMARY Merck Index
RXCUI
236558
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PRIMARY RxNorm