Identification

Name
Tolnaftate
Accession Number
DB00525  (APRD01607)
Type
Small Molecule
Groups
Approved, Investigational, Vet approved
Description

Tolnaftate is a synthetic over-the-counter anti-fungal agent. It may come as a cream, powder, spray, or liquid aerosol, and is used to treat jock itch, athlete's foot and ringworm. It is sold under several brand names, most notably Tinactin and Odor Eaters.

Structure
Thumb
Synonyms
  • 2-Naphthyl N-methyl-N-(3-tolyl)thionocarbamate
  • m,N-Dimethylthiocarbanilic acid O-2-naphthyl ester
  • Methyl (3-methylphenyl)carbamothioic acid O-2-naphthalenyl ester
  • N-Methyl-N-(3-methylphenyl)-1-(naphthalen-2-yloxy)methanethioamide
  • O-2-Naphthyl m,N-dimethylthiocarbanilate
  • Separin
  • Tolnaftato
  • Tolnaftatum
  • Tolnaphthate
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Absorbine Antifungal Powder 1%Powder1 %TopicalW.F. Young, Inc.1992-12-311997-07-28Canada
Absorbine Jr Antifungal LiquidLiquid10 mgTopicalClarion Brands, Llc1999-08-18Not applicableCanada
Aftate Athlete Foot CreamCream1 g/100gTopicalSabel Med Llc2016-12-01Not applicableUs
Anti-FungalPowder.45 g/45gTopicalRij Pharmaceutical Corporation1999-03-16Not applicableUs
Anti-FungalPowder1 g/100gTopicalRugby2011-11-01Not applicableUs
AntifungalCream10 mg/1gTopicalUnifirst First Aid2002-06-302018-10-11Us
AntifungalCream1 g/100gTopicalRite Aid2005-07-232015-10-20Us
AntifungalSolution1 mg/100mLTopicalPerrigo New York Inc.2005-12-062013-08-09Us
AntifungalSpray1 g/100gTopicalRite Aid2016-05-12Not applicableUs
AntifungalCream10 mg/1gTopicalMoore Medical2012-07-16Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Absorbine Jr Antifungal LiqTolnaftate (1 g) + Menthol (200 mg)LiquidTopicalClarion Brands, Llc1994-12-31Not applicableCanada
HeeltasticTolnaftate (1 g/100g) + Dimethicone (1 g/100g)StickTopicalNeutraderm, Inc.2009-06-30Not applicableUs
Nail MDTolnaftate (100 mg/1mg) + Triclosan (20 mg/1mg)SprayTopicalOmg Medical Group, Llc2013-02-14Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Terbinafine HCl Chlortimazole and TolnaftateTolnaftate (1 g/100mL) + Clotrimazole (1 g/100mL) + Terbinafine Hydrochloride (1 g/100mL)SolutionTopicalDr Marc's Manufacturing And Sales2018-01-302018-04-18Us
International/Other Brands
Aftate / Dr. Scholl's athlete's foot spray / Genaspor / Lamisil AF / NP-27 / Odor Eaters / Pitrex / Separin / Tinactin / Tinaderm
Categories
UNII
06KB629TKV
CAS number
2398-96-1
Weight
Average: 307.409
Monoisotopic: 307.103084861
Chemical Formula
C19H17NOS
InChI Key
FUSNMLFNXJSCDI-UHFFFAOYSA-N
InChI
InChI=1S/C19H17NOS/c1-14-6-5-9-17(12-14)20(2)19(22)21-18-11-10-15-7-3-4-8-16(15)13-18/h3-13H,1-2H3
IUPAC Name
N-methyl-N-(3-methylphenyl)-1-(naphthalen-2-yloxy)methanethioamide
SMILES
CN(C(=S)OC1=CC2=CC=CC=C2C=C1)C1=CC=CC(C)=C1

Pharmacology

Indication

Tolnaftate topical is used to treat skin infections such as athlete's foot, jock itch, and ringworm infections. Tolnaftate is also used, along with other antifungals, to treat infections of the nails, scalp, palms, and soles of the feet. The powder and powder aerosol may be used to prevent athlete's foot.

Associated Conditions
Pharmacodynamics

Tolnaftate is a synthetic over-the-counter anti-fungal agent.

Mechanism of action

Tolnaftate is a topical fungicide. Though its exact mechanism unknown, it is believed to prevent ergosterol biosynthesis by inhibiting squalene epoxidase. It has also been reported to distort the hyphae and to stunt mycelial growth in susceptible organisms.

TargetActionsOrganism
ASqualene monooxygenase
inhibitor
Yeast
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Oral rat LD50: 891 mg/kg. Inhalation rat LC50: > 900 mg/m3/1hr. Irritation: skin rabbit: 500 mg/24H mild. Eye rabbit: 100 mg severe. Investigated a mutagen and reproductive effector.

Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference

Chris E. Platt, "Topical preparation of tolnaftate and hydrocortisone to treat fungal infections of the skin." U.S. Patent US5496812, issued November, 1989.

US5496812
General References
  1. Barrett-Bee K, Dixon G: Ergosterol biosynthesis inhibition: a target for antifungal agents. Acta Biochim Pol. 1995;42(4):465-79. [PubMed:8852337]
  2. Ryder NS, Frank I, Dupont MC: Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother. 1986 May;29(5):858-60. [PubMed:3524433]
External Links
Human Metabolome Database
HMDB0005005
KEGG Drug
D00381
PubChem Compound
5510
PubChem Substance
46505456
ChemSpider
5309
BindingDB
39349
ChEBI
9620
ChEMBL
CHEMBL83668
Therapeutic Targets Database
DAP001237
PharmGKB
PA164752438
Drugs.com
Drugs.com Drug Page
Wikipedia
Tolnaftate
ATC Codes
D01AE18 — Tolnaftate
AHFS Codes
  • 84:04.08.40 — Thiocarbamates
MSDS
Download (73.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAutoimmune Diseases / Disseminated or Multiple Sclerosis Nos / Disseminated Sclerosis / Multiple Sclerosis, Acute Relapsing / Multiple Sclerosis, Chronic Progressive / Multiple Sclerosis, Primary Progressive1
2, 3Not Yet RecruitingTreatmentCandidiasis infection1
3CompletedTreatmentDermatitis, Eczematous1
3Not Yet RecruitingTreatmentICU Yeast Intra-abdominal Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Chain Drug
  • Medisca Inc.
  • Perrigo Co.
  • S&P Healthcare
  • Stiefel Labs
Dosage forms
FormRouteStrength
LiquidTopical
PowderTopical.45 g/45g
GelTopical1 %
CreamTopical0.01 mg/10g
AerosolTopical1 g/100g
CreamTopical1 g/1g
SolutionTopical1.0 mL/100mL
SolutionTopical1 mg/100mL
CreamTopical.56 g/56.69g
Solution / dropsTopical10 mg/1mL
SoapTopical1 g/100g
SolutionTopical10 mg/1mL
OilTopical0.14 g/14g
OilTopical0.3 g/28g
LotionTopical0.3 g/28g
Aerosol; powderTopical1 %
SprayTopical1 g/150g
Aerosol, foamTopical1 %
SprayTopical1 %
SolutionTopical1 g/100g
GelTopical1 g/100g
LiquidTopical10 g/1000g
GelTopical10 mg/1g
Aerosol, foamTopical10 mg/1mL
SprayTopical10 mg/1mL
SprayTopical10 mg/1g
StickTopical
OintmentTopical1 g/100g
SolutionTopical1 g/100mL
Aerosol, powderTopical0.1 g/10g
PowderTopical1 g/100g
CreamTopical0.1 g/10g
Kit10 mg/1g
SprayTopical1 g/100g
PowderTopical10 mg/1g
Aerosol, powderTopical10 mg/1g
CreamTopical0.59 g/59g
CreamTopical0.01 g/1g
OilTopical0.01 mg/1mL
LotionTopical100 g/1g
SprayTopical
LiquidTopical1 g/100mL
LiquidTopical1 mL/100mL
SolutionTopical1 %
LiquidTopical1 %
LotionTopical10 mg/1mL
SwabTopical1 %
SolutionTopical
Aerosol, sprayTopical10 mg/1g
CreamTopical10 mg
PowderTopical10 mg
AerosolTopical.72 mg
AerosolTopical1 %
LiquidTopical10 mg
LiquidTopical140 mg/15mL
Aerosol, sprayTopical1.28 g/128g
CreamTopical.2 mg/20mg
Aerosol, powderTopical1 g/100g
Aerosol, powderTopical1.1 g/113.3g
Aerosol, powderTopical1.3 g/113g
Aerosol, powderTopical1.3 g/130g
Aerosol, sprayTopical0.13 g/130g
Aerosol, sprayTopical0.15 g/150g
Aerosol, sprayTopical1.13 g/113g
Aerosol, sprayTopical1.3 g/130g
Aerosol, sprayTopical1.3 g/113g
Aerosol, sprayTopical1.5 g/150g
Aerosol, sprayTopical1.5 g/150.2g
Aerosol, sprayTopical150 g/150g
CreamTopical1 g/100g
CreamTopical10 mg/1g
SprayTopical1.3 g/130g
SprayTopical1.5 g/150g
CreamTopical1.0 %
CreamTopical1 %
LiquidTopical10 mg/1g
LiquidTopical10 mg/1mL
PowderTopical1 %
Prices
Unit descriptionCostUnit
Zeasorb-AF 2% Powder 70 gm Can14.99USD can
Zeasorb Powder 70.9 gm Can12.99USD can
Tolnaftate powder4.77USD g
Zeasorb-af 2% lotion0.19USD g
Zeasorb powder0.05USD g
Tinactin 1% aerosol0.04USD ml
Athlete's foot 1% liquid spray0.03USD g
Pv antifungal 1% spray liquid0.02USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)111 °CPhysProp
water solubility7.02e-05 mg/mL at 25 °CMEYLAN,WM et al. (1996)
logP5.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000546 mg/mLALOGPS
logP4.87ALOGPS
logP5.75ChemAxon
logS-5.8ALOGPS
pKa (Strongest Basic)0.075ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity94.92 m3·mol-1ChemAxon
Polarizability34.22 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+0.9689
Caco-2 permeable+0.6348
P-glycoprotein substrateNon-substrate0.8667
P-glycoprotein inhibitor INon-inhibitor0.5537
P-glycoprotein inhibitor IINon-inhibitor0.857
Renal organic cation transporterNon-inhibitor0.8281
CYP450 2C9 substrateNon-substrate0.7363
CYP450 2D6 substrateNon-substrate0.6071
CYP450 3A4 substrateSubstrate0.6401
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9229
Ames testAMES toxic0.8449
CarcinogenicityNon-carcinogens0.7425
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.7405 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8836
hERG inhibition (predictor II)Non-inhibitor0.5943
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
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Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-052b-0905000000-19e117da217d372632e2
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-00kb-0900000000-a065921efa544c82d972
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-0006-9600000000-19faf0e6dcd285dad8d1
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
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-c4dd1b126170bea2c620
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0900000000-b026e71179265a982a40
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0900000000-a17707ff263e82d6e00e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-3900000000-d0563822804c2844660b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-006x-9700000000-a217b6444068e1406235
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-9200000000-dc89d8219d5ce2567f3c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01ot-0901000000-c6fc83b073e80d5851f5
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Taxonomy

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
Toluenes / Thiocarbamic acid esters / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Hydrocarbon derivatives
Substituents
Naphthalene / Toluene / Monocyclic benzene moiety / Thiocarbamic acid ester / Thiocarbamic acid derivative / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Organosulfur compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
monothiocarbamic ester (CHEBI:9620)

Targets

Kind
Protein
Organism
Yeast
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
ERG1
Uniprot ID
Q92206
Uniprot Name
Squalene monooxygenase
Molecular Weight
55297.635 Da
References
  1. Barrett-Bee K, Dixon G: Ergosterol biosynthesis inhibition: a target for antifungal agents. Acta Biochim Pol. 1995;42(4):465-79. [PubMed:8852337]
  2. Ryder NS, Frank I, Dupont MC: Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate. Antimicrob Agents Chemother. 1986 May;29(5):858-60. [PubMed:3524433]
  3. Georgopapadakou NH, Bertasso A: Effects of squalene epoxidase inhibitors on Candida albicans. Antimicrob Agents Chemother. 1992 Aug;36(8):1779-81. [PubMed:1416865]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 10:02