Butenafine

Identification

Summary

Butenafine is a topical antifungal used to treat tinea versicolor, tinea pedis, tinea cruris, and tinea corporis.

Brand Names
Lotrimin Ultra, Mentax
Generic Name
Butenafine
DrugBank Accession Number
DB01091
Background

Butenafine hydrochloride is a synthetic benzylamine antifungal agent. Butenafine's mechanism of action is believed to involve the synthesis inhibition of sterols. In particular, butenafine acts to inhibit the activity of the squalene epoxidase enzyme that is essential in the formation of sterols necessary for fungal cell membranes.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 317.4672
Monoisotopic: 317.214349869
Chemical Formula
C23H27N
Synonyms
  • (4-tert-Butyl-benzyl)-methyl-naphthalen-1-ylmethyl-amine
  • (4-tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)methanamine
  • 4-tert-butylbenzyl(methyl)(1-naphthalenemethyl)amine
  • Butenafina
  • Butenafine
  • Butenafinum
  • N-(p-tert-butylbenzyl)-N-methyl-1-naphthalenemethylamine

Pharmacology

Indication

For the topical treatment of the following dermatologic infections: tinea (pityriasis) versicolor due to M. furfur, interdigital tinea pedis (athlete’s foot), tinea corporis (ringworm) and tinea cruris (jock itch) due to E. floccosum, T. mentagrophytes, T. rubrum, and T. tonsurans.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
ASqualene monooxygenase
inhibitor
Humans
Absorption

The total amount absorbed through the skin into the systemic circulation has not been quantified.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

The primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain.

Route of elimination

Not Available

Half-life

Following topical application, a biphasic decline of plasma butenafine concentrations was observed with the half-lives estimated to be 35 hours initial and over 150 hours terminal.

Clearance

Not Available

Adverse Effects
Medicalerrors
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Butenafine hydrochlorideR8XA2029ZI101827-46-7LJBSAUIFGPSHCN-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MentaxCream10 mg/1gTopicalBERTEK PHARMACEUTICALS INC.2006-01-202006-07-18US flag
MentaxCream10 mg/1gTopicalMylan Pharmaceuticals Inc.1996-12-31Not applicableUS flag
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Athletes FootCream10 mg/1gTopicalTarget Corporation.2017-11-17Not applicableUS flag
Athletes FootCream10 mg/1gTopicalWalgreen2017-11-17Not applicableUS flag
Athletes FootCream10 mg/1gTopicalCVS PHARMACY2017-11-17Not applicableUS flag
Athletes FootCream10 mg/1gTopicalTopco Associates LLC2017-11-17Not applicableUS flag
Athletes FootCream10 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2017-11-17Not applicableUS flag
Athletes FootCream10 mg/1gTopicalRite Aid2017-11-17Not applicableUS flag
Athletes Foot UltraCream10 mg/1gTopicalWAL-MART STORES INC2017-11-16Not applicableUS flag
Athletes Foot UltraCream10 mg/1gTopicalH.E.B.2017-11-17Not applicableUS flag
Butenafine Hydrochloride 1%Cream10 mg/1gTopicalCVS PHARMACY2018-10-18Not applicableUS flag
Butenafine Hydrochloride Athletes FootCream10 mg/1gTopicalKroger Company2017-11-16Not applicableUS flag

Categories

ATC Codes
D01AE23 — Butenafine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Not Available
Direct Parent
Naphthalenes
Alternative Parents
Phenylpropanes / Phenylmethylamines / Benzylamines / Aralkylamines / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aralkylamine / Aromatic homopolycyclic compound / Benzylamine / Hydrocarbon derivative / Monocyclic benzene moiety / Naphthalene / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tertiary amine, naphthalenes (CHEBI:3238)
Affected organisms
  • Fungi

Chemical Identifiers

UNII
91Y494NL0X
CAS number
101828-21-1
InChI Key
ABJKWBDEJIDSJZ-UHFFFAOYSA-N
InChI
InChI=1S/C23H27N/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
IUPAC Name
[(4-tert-butylphenyl)methyl](methyl)(naphthalen-1-ylmethyl)amine
SMILES
CN(CC1=CC=C(C=C1)C(C)(C)C)CC1=CC=CC2=CC=CC=C12

References

Synthesis Reference
US5021458
General References
  1. McNeely W, Spencer CM: Butenafine. Drugs. 1998 Mar;55(3):405-12; discussion 413. [Article]
  2. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. doi: 10.1517/17425255.4.7.999 . [Article]
  3. Gupta AK: Butenafine: an update of its use in superficial mycoses. Skin Therapy Lett. 2002 Sep;7(7):1-2, 5. [Article]
  4. Mingeot-Leclercq MP, Gallet X, Flore C, Van Bambeke F, Peuvot J, Brasseur R: Experimental and conformational analyses of interactions between butenafine and lipids. Antimicrob Agents Chemother. 2001 Dec;45(12):3347-54. [Article]
  5. Syed TA, Maibach HI: Butenafine hydrochloride: for the treatment of interdigital tinea pedis. Expert Opin Pharmacother. 2000 Mar;1(3):467-73. [Article]
  6. Reyes BA, Beutner KR, Cullen SI, Rosen T, Shupack JL, Weinstein MB: Butenafine, a fungicidal benzylamine derivative, used once daily for the treatment of interdigital tinea pedis. Int J Dermatol. 1998 Jun;37(6):450-3. [Article]
  7. Iwatani W, Arika T, Yamaguchi H: Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993 Apr;37(4):785-8. [Article]
Human Metabolome Database
HMDB0015223
KEGG Drug
D07596
KEGG Compound
C08067
PubChem Compound
2484
PubChem Substance
46506191
ChemSpider
2390
BindingDB
50436713
RxNav
47461
ChEBI
3238
ChEMBL
CHEMBL990
ZINC
ZINC000001530975
Therapeutic Targets Database
DAP001236
PharmGKB
PA164745478
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Butenafine
AHFS Codes
  • 84:04.08.12 — Benzylamines
FDA label
Download (1.39 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentDermatitis, Photoallergic1
3CompletedTreatmentDermatitis, Phototoxic1
3CompletedTreatmentHypersensitivity2
2RecruitingTreatmentTinea Pedis1
1CompletedTreatmentTinea Pedis2
1TerminatedTreatmentInterdigital Tinea Pedis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Erregierre SPA
  • Mylan
  • Schering-Plough Inc.
Dosage Forms
FormRouteStrength
LotionTopical
CreamTopical
SprayTopical
CreamTopical1 %
CreamTopical1 g/100g
CreamTopical10 mg/1g
Prices
Unit descriptionCostUnit
Mentax 1% Cream 30 gm Tube124.7USD tube
Mentax 1% Cream 15 gm Tube50.99USD tube
Mentax 1% cream4.0USD g
Lotrimin ultra 1% cream0.68USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5021458No1991-06-042010-10-18US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly soluble (HCl salt)Not Available
logP6.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.56e-05 mg/mLALOGPS
logP5.85ALOGPS
logP6.17ChemAxon
logS-6.6ALOGPS
pKa (Strongest Basic)9.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity104.33 m3·mol-1ChemAxon
Polarizability38.41 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9904
Blood Brain Barrier+0.9514
Caco-2 permeable+0.7822
P-glycoprotein substrateSubstrate0.5855
P-glycoprotein inhibitor INon-inhibitor0.8215
P-glycoprotein inhibitor IIInhibitor0.7052
Renal organic cation transporterNon-inhibitor0.5078
CYP450 2C9 substrateNon-substrate0.8124
CYP450 2D6 substrateNon-substrate0.8686
CYP450 3A4 substrateSubstrate0.6225
CYP450 1A2 substrateNon-inhibitor0.6056
CYP450 2C9 inhibitorNon-inhibitor0.9401
CYP450 2D6 inhibitorInhibitor0.8189
CYP450 2C19 inhibitorNon-inhibitor0.666
CYP450 3A4 inhibitorNon-inhibitor0.7581
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6169
Ames testNon AMES toxic0.9008
CarcinogenicityCarcinogens 0.5115
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.2204 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8911
hERG inhibition (predictor II)Inhibitor0.5849
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Squalene monooxygenase activity
Specific Function
Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
Gene Name
SQLE
Uniprot ID
Q14534
Uniprot Name
Squalene monooxygenase
Molecular Weight
63922.505 Da
References
  1. Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA: Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother. 2003 Jan;47(1):82-6. [Article]
  2. Gao PH, Cao YB, Xu Z, Zhang JD, Zhang WN, Wang Y, Gu J, Cao YY, Li RY, Jia XM, Jiang YY: 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. Biol Pharm Bull. 2005 Aug;28(8):1414-7. [Article]
  3. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. doi: 10.1517/17425255.4.7.999 . [Article]
  4. Ramam M, Prasad HR, Manchanda Y, Khaitan BK, Banerjee U, Mukhopadhyaya A, Shetty R, Gogtay JA: Randomised controlled trial of topical butenafine in tinea cruris and tinea corporis. Indian J Dermatol Venereol Leprol. 2003 Mar-Apr;69(2):154-8. [Article]
  5. Iwatani W, Arika T, Yamaguchi H: Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993 Apr;37(4):785-8. [Article]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Drug created on June 13, 2005 13:24 / Updated on June 23, 2021 06:08