Menthyl salicylate

Identification

Brand Names
Max-freeze
Generic Name
Menthyl salicylate
DrugBank Accession Number
DB11201
Background

Menthyl salicylate is an ester of menthol and salicylic acid 1.

This product is used to treat minor aches and pains of the muscles/joints (e.g., arthritis, backache, sprains) 2.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 276.376
Monoisotopic: 276.172544633
Chemical Formula
C17H24O3
Synonyms
  • 1-Menthyl salicylate
  • Menthyl salicylate, (+/-)-

Pharmacology

Indication

For the temporary relief of pain associated with rheumatism, arthritis, neuralgia, sprains and strains of joints and muscles, lumbago and fibrositis 7.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Menthol and methyl salicylate are known as counterirritants. They work by causing the skin to feel cool and then warm. Used together, they provide symptomatic relief for mild to moderate muscular and joint aches and pains, muscle cramps, shoulder aches and stiff neck.2.

Mechanism of action

Menthol dilates the blood vessels causing a sensation of coldness, followed by an analgesic effect. Menthol also acts as a penetration enhancer, increasing the penetration of drugs when applied on the skin, to give a faster onset of action 6.

Methyl salicylate is a salicylic acid derivative, and when combined with menthol, produces menthyl salicylate 6.

Salicylates inhibit cyclooxygenase, thereby reducing the formation of prostaglandins, and cause platelet dysfunction Methyl salicylate is used topically as a counter-irritant. Upon application, it is absorbed through the skin and is applied for the relief of pain in rheumatic conditions and painful muscle or joints 6.

The menthol dilates blood vessels, why the salicylate portion provides a topical anesthetic and analgesic action on the affected area. The cooling and warning action may interfere with the transmission of pain signals through nerves 6.

TargetActionsOrganism
UBlood vessels
antagonist
dilator
Humans
AProstaglandin G/H synthase 1
antagonist
Humans
AProstaglandin G/H synthase 2
antagonist
Humans
Absorption

May be absorbed through intact skin. The absorption of topical salicylates is proportional to the surface area exposed, the duration of exposure, concentration and skin integrity. Absorption characteristics of salicylates vary with the dose, formulation, and route of administration. Percutaneous absorption is enhanced by exercise, heat, occlusion, or disruption of the integrity of the skin or application to large areas of skin. Both the rate and extent of absorption increases after continuous application, increasing its bioavailability 7.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Salicylate intoxication may occur after ingestion or topical application of menthyl salicylate. Mild chronic salicylate intoxication, also known as salicylism, normally occurs only after repeated use of large doses.

Salicylism can also occur following the excessive topical application of salicylates. Symptoms of toxicity include dizziness, tinnitus, deafness, sweating, nausea and vomiting, headache, and confusion, and may be controlled by reducing the dosage 7.

Symptoms of more severe intoxication or of acute poisoning following overdose include hyperventilation, fever, restlessness, ketosis, and respiratory alkalosis and metabolic acidosis. Depression of the CNS may lead to coma, cardiovascular collapse and respiratory failure may also result 7.

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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Active Moieties
NameKindUNIICASInChI Key
Salicylic acidunknownO414PZ4LPZ69-72-7YGSDEFSMJLZEOE-UHFFFAOYSA-N
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Calmomusc LiqMenthyl salicylate (6.3 %) + Eucalyptol (2.1 %) + Levomenthol (3.17 %)LiquidTopicalCardinaux Enrg Les Produits Naturels1989-12-312000-07-07Canada flag
Dr. Ds Super 7 Pain ReliefMenthyl salicylate (100 mg/1mL) + Levomenthol (20 mg/1mL)CreamTopicalPromedx Innovations Inc2019-09-04Not applicableUS flag
Extra Strength Hua Tuo Medicated PlasterMenthyl salicylate (13.84 g/1) + Levomenthol (3.32 g/1) + Synthetic camphor (8.3 g/1)PlasterTopical; TransdermalGuangzhou Baiyunshan Jingxiutang Pharmaceutical Company2013-06-17Not applicableUS flag
Flexall StickMenthyl salicylate (30 %) + Levomenthol (10 %)StickTopicalChattem, Inc.1997-08-072003-06-06Canada flag
Muscle Rub UltraMenthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Levomenthol (10 g/100g)CreamTopicalKareway Product, Inc.2011-08-11Not applicableUS flag
Muscle Rub UltraMenthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Levomenthol (10 g/100g)CreamTopicalNeopharm Co., Ltd2010-08-16Not applicableUS flag
Muscle Rub UltraMenthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Levomenthol (10 g/100g)CreamTopicalH E B2011-07-25Not applicableUS flag
Pain Relief PatchMenthyl salicylate (5 g/100g) + Capsaicin (0.025 g/100g) + Levomenthol (5 g/100g)PatchTopicalHangzhou Jujiu Science & Biotechnology Co.,ltd.2015-07-10Not applicableUS flag
Pain Relief RubMenthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Levomenthol (10 g/100g)CreamTopicalTopco Associates2013-09-01Not applicableUS flag
Pain Relief RubMenthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Levomenthol (10 g/100g)CreamTopicalDiscount Drug Mart2015-11-09Not applicableUS flag

Categories

Drug Categories
Not Available
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as o-hydroxybenzoic acid esters. These are benzoic acid esters where the benzene ring is ortho-substituted with a hydroxy group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
o-Hydroxybenzoic acid esters
Alternative Parents
Salicylic acid and derivatives / Monocyclic monoterpenoids / Menthane monoterpenoids / Aromatic monoterpenoids / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Carboxylic acid esters / Monocarboxylic acids and derivatives
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Substituents
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Aromatic homomonocyclic compound / Aromatic monoterpenoid / Benzoyl / Carboxylic acid derivative / Carboxylic acid ester / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Monocyclic monoterpenoid
show 9 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans

Chemical Identifiers

UNII
43XOA705ZD
CAS number
89-46-3
InChI Key
SJOXEWUZWQYCGL-DVOMOZLQSA-N
InChI
InChI=1S/C17H24O3/c1-11(2)13-9-8-12(3)10-16(13)20-17(19)14-6-4-5-7-15(14)18/h4-7,11-13,16,18H,8-10H2,1-3H3/t12-,13+,16-/m1/s1
IUPAC Name
(1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl 2-hydroxybenzoate
SMILES
CC(C)[C@@H]1CC[C@@H](C)C[C@H]1OC(=O)C1=CC=CC=C1O

References

General References
  1. Menthyl Salicylate, EWG [Link]
  2. Menthyl Salicylate [Link]
  3. Salicylate toxicity [Link]
  4. Best Practice BMJ, Salicylate poisoning [Link]
  5. Salicylate poisoning, patient info [Link]
  6. Medicine.net: menthol and methylsalicylate [Link]
  7. Drug Insert [File]
ChemSpider
16736426
RxNav
1368207
ChEBI
135976
ZINC
ZINC000000002060
MSDS
Download (52.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
LiquidTopical
PlasterTopical; Transdermal
StickTopical
CreamTopical
PatchTopical
OintmentTopical
GelTopical
PatchTransdermal
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)186MSDS
logP4.01https://www.chemeo.com/cid/67-677-7/Menthyl%20salicylate
Predicted Properties
PropertyValueSource
Water Solubility0.0275 mg/mLALOGPS
logP4.24ALOGPS
logP5.51ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)9.72ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity79.25 m3·mol-1ChemAxon
Polarizability31.14 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

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

Drugtargets2
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1. Blood vessels
Kind
Group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Dilator
References
  1. Dolen UC, Sungur N, Koca G, Ertunc O, Bagci Bosi AT, Kocer U, Korkmaz M: The Vasodilator Effect of a Cream Containing 10% Menthol and 15% Methyl Salicylate on Random-Pattern Skin Flaps in Rats. Arch Plast Surg. 2015 Nov;42(6):695-703. doi: 10.5999/aps.2015.42.6.695. Epub 2015 Nov 16. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Cronstein BN, Montesinos MC, Weissmann G: Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFkappaB. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6377-81. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Cronstein BN, Montesinos MC, Weissmann G: Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFkappaB. Proc Natl Acad Sci U S A. 1999 May 25;96(11):6377-81. [Article]

Drug created on December 03, 2015 16:51 / Updated on June 12, 2020 16:53