Identification
- Summary
Methyl salicylate is a topical counter-irritant used for the symptomatic relief of acute musculoskeletal pain in the muscles, joints, and tendons.
- Brand Names
- Dendracin Neurodendraxcin, Flexall Ultra Plus, Lidopro, Listerine Antiseptic, Medi-derm, Medi-derm With Lidocaine, Medrox, Mentholatum, Rematex, Salonpas Pain Relieving Patch, Tiger Balm, Xoten-C
- Generic Name
- Methyl salicylate
- DrugBank Accession Number
- DB09543
- Background
Methyl salicylate (oil of wintergreen or wintergreen oil) is an organic ester naturally produced by many species of plants, particularly wintergreens. The compound was first extracted and isolated from plant species Gaultheria procumbens in 1843. It can be manufactured synthetically and it used as a fragrance, in foods, beverages, and liniments. It forms a colorless to yellow or reddish liquid and exhibits a characteristic odor and taste of wintergreen. For acute joint and muscular pain, methyl salicylate is used as a rubefacient and analgesic in deep heating liniments. It is used as a flavoring agent in chewing gums and mints in small concentrations and added as antiseptic in mouthwash solutions.
- Type
- Small Molecule
- Groups
- Approved, Vet approved
- Structure
Structure for Methyl salicylate (DB09543)
- Weight
- Average: 152.1473
Monoisotopic: 152.047344122 - Chemical Formula
- C8H8O3
- Synonyms
- 2-(Methoxycarbonyl)phenol
- 2-Carbomethoxyphenol
- 2-Hydroxybenzoic acid methyl ester
- Betula oil
- Gaultheria oil
- Methyl 2-hydroxybenzoate
- Methyl o-hydroxybenzoate
- Methyl salicylate
- Natural wintergreen oil
- Oil of wintergreen
- Spicewood Oil
- Sweet birch oil
- Teaberry oil
Pharmacology
- Indication
Ointments or liniments containing methyl salicylate are applied topically as counter irritant for relief of acute pain associated with lumbago,sciatica and rheumatic conditions. Local analgesics for human and veterinary medicine.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Acute muscle pain Combination Product in combination with: Piroxicam (DB00554), Eugenol (DB09086), Levomenthol (DB00825) ••• ••• ••• Used in combination for symptomatic treatment of Arthritis Combination Product in combination with: Levomenthol (DB00825), Camphor (DB01744), Eucalyptus oil (DB11114) ••• ••• •••••••• Used as adjunct in combination to treat Back pain lower back Combination Product in combination with: Levomenthol (DB00825), Chlorobutanol (DB11386), Camphor (DB01744) ••• ••• •••••••• Used in combination to treat Back pain lower back Combination Product in combination with: Camphor (DB01744), Levomenthol (DB00825), Eucalyptus oil (DB11114) ••• ••• ••• Used in combination to treat Backache Combination Product in combination with: Levomenthol (DB00825), Eucalyptus oil (DB11114), Camphor (DB01744) ••• ••• •••••••• - Contraindications & Blackbox Warnings
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Methyl salicylate relieve musculoskeletal pain in the muscles, joints, and tendons by causing irritation and reddening of the skin due to dilated capillaries and increased blood flow. It is pharmacologically similar to aspirin and other NSAIDs but as a topical agent it primarily acts as a rubefacient and skin irritant. Counter-irritation is believed to cause a soothing sensation of warmth.
- Mechanism of action
Counter-irritation is thought to be effective at alleviating musculoskeletal pain as the irritation of the sensory nerve endings is thought to alter or offset pain in the underlying muscle or joints that are served by the same nerves 5. This is thought to mask the underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and underlying tissues where it reversibly inhibits cyclooxygenase enzyme and locally and peripherally prevents the production of inflammatory mediators such as prostaglandin and thromboxane A2.
- Absorption
Approximately 12-20% of topically applied methyl salicylate may be systemically absorbed through intact skin within 10 hours of application, and absorption varies with different conditions such as surface area and pH. Dermal bioavailability is in the range of 11.8 – 30.7%. For the assessment of potential oral exposure to salicylates, bioavailability is assumed to be 100% 9.
- Volume of distribution
After absorption, methyl salicylate is distributed throughout most body tissues and most transcellular fluids, primarily by pH dependent passive processes. Salicylate is actively transported by a low-capacity, saturable system out of the CSF across the choroid plexus. The drug readily crosses the placental barrier.
- Protein binding
Degree of albumin binding depends on the plasma concentration of the compound
- Metabolism
Minor metabolism may occur in various tissues but hepatic metabolism constitutes the majority of metabolic processes of absorbed methyl salicylate. It is mainly hydrolyzed to salicylic acid via hepatic esterase enzymes. Conjugation with glycine forms salicyluric acid and conjugation with glucuronic forms ester or acyl and ether or phenolic glucuronide, which are the three main metabolites.
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- Route of elimination
Excreted by kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl glucuronide (5%), and gentisic acid (less than 1%).
- Half-life
The plasma half-life for salicylate is 2 to 3 hr in low doses and about 12 hr at usual anti-inflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication.
- Clearance
Not Available
- Adverse Effects
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Oral LD50 values (mg/kg) for mouse, rat and rabbit are 1110, 887 and 1300, respectively. Oral LD50 values for child and adult human (mg/kg) are 228 and 506, respectively. Although systemic toxicity from topical administration is rare, methyl salicylate can be absorbed in intract skin to cause stimulation of the central nervous system respiratory center, disturbance of lipid and carbohydrate metabolism, and disturbance of intracellular respiration. Severe toxicity can result in acute lung injury, lethargy, coma, seizures, cerebral edema, and death. In case of salicylate poisoning, the treatment consists of general supportive care, gastrointestinal decontamination with activated charcoal in cases of salicylate ingestion, and monitoring of serum salicylate concentrations. Bicarbonate infusions or hemodialysis can be used to achieve enhanced salicylate elimination 7.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of bleeding can be increased when Methyl salicylate is combined with Abciximab. Acarbose Methyl salicylate may increase the hypoglycemic activities of Acarbose. Aceclofenac The therapeutic efficacy of Methyl salicylate can be decreased when used in combination with Aceclofenac. Acenocoumarol Methyl salicylate may increase the anticoagulant activities of Acenocoumarol. Acetaminophen The risk or severity of adverse effects can be increased when Acetaminophen is combined with Methyl salicylate. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Active Moieties
Name Kind UNII CAS InChI Key Salicylic acid unknown O414PZ4LPZ 69-72-7 YGSDEFSMJLZEOE-UHFFFAOYSA-N - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Abejas y Viboras Roll On Liquid 10 g/100g Topical MENPER DISTRIBUTORS INC. 2021-03-31 Not applicable US 
Activ-Rub Liniment Liniment Topical WINWA MEDICAL SDN. BHD. 2020-09-08 Not applicable Malaysia 
ANTIFLAM RUB Cream Topical PRIME PHARMACEUTICAL SDN. BHD. 2020-09-08 Not applicable Malaysia ANTIPAIN LINIMENT 25% Liniment Topical ZONTRON PHARMACEUTICALS SDN. BHD. 2020-09-08 Not applicable Malaysia Aspi-Rub Pain Reliever Spray 23 g/100g Topical AspiRub Enterprises LLC 2014-08-29 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 1st Medxpatch With Lidocaine 4% Methyl salicylate (20 g/1) + Capsaicin (0.025 g/1) + Lidocaine (4 g/1) + Menthol (5 g/1) Patch Topical 1ST MEDX LLC 2018-03-15 Not applicable US 365 Whole Foods Market Anticavity/Antigingivitis Mouthwash Methyl salicylate (0.6 mg/1mL) + Eucalyptol (0.92 mg/1mL) + Menthol (0.42 mg/1mL) + Sodium fluoride (0.1 mg/1mL) + Thymol (0.64 mg/1mL) Mouthwash Dental Whole Foods Market, Inc. 2022-01-31 Not applicable US 365 Whole Foods Market Antigingivitis Mouthwash Methyl salicylate (0.6 mg/1mL) + Eucalyptol (0.92 mg/1mL) + Menthol (0.42 mg/1mL) + Thymol (0.64 mg/1mL) Mouthwash Dental Whole Foods Market, Inc. 2022-01-31 Not applicable US 701 Dieda Zhengtong Yaogao Medicated Methyl salicylate (10 g/1) + Menthol (8 g/1) + Synthetic camphor (3.1 g/1) Plaster Topical; Transdermal GUANGZHOU BAIYUNSHAN PHARMACEUTICAL CO., LTD. BAIYUNSHAN HEJIGONG PHARMACEUTICAL FACTORY 2001-10-15 Not applicable US AA Top Medicated Methyl salicylate (0.05 g/1mL) + Menthol (0.1 g/1mL) Oil Topical Albert Max, Inc. 2018-02-01 Not applicable US - Unapproved/Other Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image 1st Medxpatch With Lidocaine 4%-rx Methyl salicylate (20 g/1) + Capsaicin (0.0375 g/1) + Lidocaine (4 g/1) + Menthol (5 g/1) Patch Topical 1ST MEDX LLC 2018-03-15 Not applicable US 1st Medxpatch With Lidocaine 4%-rx Methyl salicylate (20 1/1) + Capsaicin (0.0375 1/1) + Lidocaine (4 1/1) + Menthol (5 1/1) Patch Topical Direct Rx 2020-10-14 Not applicable US Adazin Methyl salicylate (1 g/100g) + Benzocaine (2 g/100g) + Capsaicin (0.035 g/100g) + Lidocaine (2 g/100g) Cream Topical Sterling Knight Pharmaceuticals, Llc 2014-12-03 2018-10-01 US AMULDY SPORTS gel Methyl salicylate (0.3 g/100mL) + Camphor (0.05 g/100mL) + Menthol (2.5 g/100mL) + Salicylic acid (0.03 g/100mL) Liquid Topical Lydia Co., Ltd. 2020-04-24 Not applicable US Anesthall Pain Relieving Cream Methyl salicylate (6.1 g/100g) + Menthol (4.6 g/100g) Cream Topical Advanced Pharmaceutics Inc 2023-12-11 Not applicable US
Categories
- Drug Categories
- Acids, Carbocyclic
- Analgesics
- Antirheumatic Agents
- Benzene Derivatives
- Benzoates
- Betula
- Biological Products
- Complex Mixtures
- Compounds used in a research, industrial, or household setting
- Fixatives
- Gaultheria
- Hydroxy Acids
- Hydroxybenzoates
- Lipids
- Oils
- Pharmaceutical Preparations
- Phenols
- Plant Preparations
- Salicylates
- 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 / Benzoyl derivatives / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids / Vinylogous acids / Methyl esters / Monocarboxylic acids and derivatives / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Aromatic homomonocyclic compound / Benzoyl / Carboxylic acid derivative / Carboxylic acid ester / Hydrocarbon derivative / Methyl ester / Monocarboxylic acid or derivatives / O-hydroxybenzoic acid ester
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- salicylates, benzoate ester (CHEBI:31832) / a small molecule (CPD-6442)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- LAV5U5022Y
- CAS number
- 119-36-8
- InChI Key
- OSWPMRLSEDHDFF-UHFFFAOYSA-N
- InChI
- InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3
- IUPAC Name
- methyl 2-hydroxybenzoate
- SMILES
- COC(=O)C1=CC=CC=C1O
References
- General References
- He YY, Yan Y, Zhang HF, Lin YH, Chen YC, Yan Y, Wu P, Fang JS, Yang SH, Du GH: Methyl salicylate 2-O-beta-d-lactoside alleviates the pathological progression of pristane-induced systemic lupus erythematosus-like disease in mice via suppression of inflammatory response and signal transduction. Drug Des Devel Ther. 2016 Sep 29;10:3183-3196. eCollection 2016. [Article]
- Xin W, Huang C, Zhang X, Xin S, Zhou Y, Ma X, Zhang D, Li Y, Zhou S, Zhang D, Zhang T, Du G: Methyl salicylate lactoside inhibits inflammatory response of fibroblast-like synoviocytes and joint destruction in collagen-induced arthritis in mice. Br J Pharmacol. 2014 Jul;171(14):3526-38. doi: 10.1111/bph.12715. [Article]
- Mason L, Moore RA, Edwards JE, McQuay HJ, Derry S, Wiffen PJ: Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain. BMJ. 2004 Apr 24;328(7446):995. Epub 2004 Mar 19. [Article]
- Higashi Y, Kiuchi T, Furuta K: Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study. Clin Ther. 2010 Jan;32(1):34-43. doi: 10.1016/j.clinthera.2010.01.016. [Article]
- Derry S, Matthews PR, Wiffen PJ, Moore RA: Salicylate-containing rubefacients for acute and chronic musculoskeletal pain in adults. Cochrane Database Syst Rev. 2014 Nov 26;(11):CD007403. doi: 10.1002/14651858.CD007403.pub3. [Article]
- Moore RA, Derry S, McQuay HJ: Topical analgesics for acute and chronic pain in adults. Cochrane Database Syst Rev. 2010;(7). pii: CD008609. [Article]
- Thompson TM, Toerne T, Erickson TB: Salicylate Toxicity from Genital Exposure to a Methylsalicylate-Containing Rubefacient. West J Emerg Med. 2016 Mar;17(2):181-3. doi: 10.5811/westjem.2016.1.29262. Epub 2016 Mar 2. [Article]
- FDA SALONPAS® Pain Relief Patch Clinical Review [Link]
- Norwegian Food Safety Authority: Methyl salicylate risk review [Link]
- External Links
- Human Metabolome Database
- HMDB0034172
- KEGG Drug
- D01087
- KEGG Compound
- C12305
- PubChem Compound
- 4133
- PubChem Substance
- 347827876
- ChemSpider
- 13848808
- 29787
- ChEBI
- 31832
- ChEMBL
- CHEMBL108545
- ZINC
- ZINC000000000490
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Methyl_salicylate
- MSDS
- Download (55.2 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Prevention Healthy Subjects (HS) 1 4 Completed Treatment Chronic Lower Back Pain (CLBP) 2 4 Completed Treatment Sub-acute Back Pain 1 3 Not Yet Recruiting Treatment Pain 1 3 Recruiting Treatment Migraine 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Mouthwash Buccal; Dental Aerosol, spray Percutaneous; Topical; Transdermal Aerosol, spray Cutaneous; Topical; Transdermal Spray Topical Ointment Enteral Cream Topical Liniment Topical Mouthwash Oral Spray Topical 23 g/100g Mouthwash Buccal Ointment Topical 10.5 g/90g Solution Topical Oil Percutaneous; Topical; Transdermal Ointment Cutaneous Powder Topical Solution Transdermal 3 g/100mL Spray Topical 60 mg/1mL Oil Lotion Topical 10 g/100mL Lotion Topical 10 g/1g Mouthwash Dental Gel Transdermal Patch Transdermal Ointment Topical Plaster Transdermal Cream Topical 7 g Kit Topical Liniment Topical Liquid Dental Salve Topical Solution Buccal; Oral Plaster Liquid Topical 15 g/100g Crystal Topical Cream Topical 250 mg/1mL Ointment Topical 100 mg/1mL Ointment Topical 20 mg/1mL Patch Cutaneous; Topical; Transdermal Solution, concentrate Oral Paste Topical Stick Topical .25 g/1g Liniment Topical 25 % Liquid Topical 980 mg/1mL Plaster Topical 1 g/1 Oil Topical 60 g/100mL Ointment Topical 13.5 g/100g Kit Oral; Topical Stick Topical Liquid Respiratory (inhalation) Liquid Topical Ointment Topical 10.5 g/100g Ointment Topical 15 g/100g Ointment Topical 12 g/100g Ointment Topical 15 g/113g Ointment Topical 12 g/113g Oil Topical 25 g/100mL Rinse Oral Oil Topical 105 mg/1mL Solution Topical 25 %v/v Inhalant Nasal Cream Topical 250 mg/1g Patch Topical 100 mg/1000mg Patch Topical 10 g/1 Ointment Topical Ointment Topical 10 g/100g Spray Oral Cream Topical Jelly Nasal Gel Topical 105 mg/1g Lotion Topical 20 g/100g Capsule; kit; liquid Oral; Topical Kit Oral Patch Topical Liquid Oral Liquid Cutaneous Patch Topical; Transdermal Kit; patch Topical Patch Percutaneous; Topical; Transdermal Oil Topical Liquid Topical 40 g/100mL Lotion Topical 0.95 % Gel Percutaneous; Topical; Transdermal Spray Cutaneous Aerosol, foam Percutaneous; Topical; Transdermal Ointment Percutaneous; Topical; Transdermal Aerosol, spray Topical Liquid Cutaneous; Topical; Transdermal Liquid Topical 10 g/100g Patch Topical 10 mg/100mg Patch Topical 10 g/100g Emulsion Topical 10 % Lotion Topical 0.95 % w/v Stick Topical 10 g/100mL Cream Topical 100 mg/1g Cream Topical 10 g/100g Gel Topical Lotion Topical Emulsion Topical 15 g/100g Ointment Topical 15 mg/100g Ointment Topical 5 mg/100g Cream Cutaneous Aerosol Topical Gel Topical 100 mg/1g Ointment Topical 10 g Liniment Topical 25 g/100ml Cream; kit; solution Topical Ointment Topical 15.75 g/150g Liquid Topical 12 g/100mL Liquid Topical 12 mg/100mL Liquid Topical 7 g/100mL Oil Transdermal Liquid Topical Plaster Topical; Transdermal Cream Topical 10 g/100mL Plaster Topical Poultice Transdermal 160 mg/17g Poultice Transdermal 105 mg/17.5g Liquid Topical 200 mg/1g Solution Oral Oil Topical 100 ml/100ml Oil Topical 35 ml/100ml Oil Topical 36 ml/100ml Emulsion Topical 5 ml/100ml Cream Topical 14 %w/w Emulsion Topical Cream Topical 12 %w/w - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8809615 No 2014-08-19 2030-01-03 US US9233184 No 2016-01-12 2027-08-01 US
Properties
- State
- Liquid
- Experimental Properties
Property Value Source melting point (°C) -8.6 MSDS boiling point (°C) 220-224 MSDS water solubility Slightly soluble MSDS logP 2.5 MSDS - Predicted Properties
Property Value Source Water Solubility 5.73 mg/mL ALOGPS logP 2.07 ALOGPS logP 2.32 Chemaxon logS -1.4 ALOGPS pKa (Strongest Acidic) 9.72 Chemaxon pKa (Strongest Basic) -4.3 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 46.53 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 40.06 m3·mol-1 Chemaxon Polarizability 14.98 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 132.2217102 predictedDarkChem Lite v0.1.0 [M-H]- 131.7101102 predictedDarkChem Lite v0.1.0 [M-H]- 132.2150102 predictedDarkChem Lite v0.1.0 [M-H]- 132.1670102 predictedDarkChem Lite v0.1.0 [M-H]- 129.27269 predictedDeepCCS 1.0 (2019) [M+H]+ 132.7134102 predictedDarkChem Lite v0.1.0 [M+H]+ 131.8589102 predictedDarkChem Lite v0.1.0 [M+H]+ 133.0046102 predictedDarkChem Lite v0.1.0 [M+H]+ 132.7290102 predictedDarkChem Lite v0.1.0 [M+H]+ 133.04425 predictedDeepCCS 1.0 (2019) [M+Na]+ 132.4824102 predictedDarkChem Lite v0.1.0 [M+Na]+ 131.7454102 predictedDarkChem Lite v0.1.0 [M+Na]+ 132.3076102 predictedDarkChem Lite v0.1.0 [M+Na]+ 132.3778102 predictedDarkChem Lite v0.1.0 [M+Na]+ 142.29716 predictedDeepCCS 1.0 (2019)
Drug created at November 30, 2015 19:10 / Updated at February 20, 2024 23:55