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

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level
Used in combination for symptomatic treatment of	Arthritis	Combination Product in combination with: Levomenthol (DB00825)	••• •••
Used in combination for symptomatic treatment of	Arthritis	Combination Product in combination with: Levomenthol (DB00825), Camphor (DB01744)	••• •••
Used in combination for symptomatic treatment of	Back pain	Combination Product in combination with: Levomenthol (DB00825)	••• •••
Used in combination for symptomatic treatment of	Back pain	Combination Product in combination with: Camphor (DB01744), Levomenthol (DB00825)	••• •••
Used in combination for symptomatic treatment of	Contusions	Combination Product in combination with: Levomenthol (DB00825)	••• •••

Contraindications & Blackbox Warnings

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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.

Target	Actions	Organism
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

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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.

Drug	Interaction
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Abciximab	The risk or severity of bleeding and hemorrhage can be increased when Menthyl salicylate is combined with Abciximab.
Acebutolol	Menthyl salicylate may decrease the antihypertensive activities of Acebutolol.
Aceclofenac	The risk or severity of adverse effects can be increased when Aceclofenac is combined with Menthyl salicylate.
Acemetacin	The risk or severity of adverse effects can be increased when Menthyl salicylate is combined with Acemetacin.
Acenocoumarol	The risk or severity of bleeding and hemorrhage can be increased when Menthyl salicylate is combined with Acenocoumarol.

Food Interactions

No interactions found.

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Active Moieties

Name	Kind	UNII	CAS	InChI Key
Salicylic acid	unknown	O414PZ4LPZ	69-72-7	YGSDEFSMJLZEOE-UHFFFAOYSA-N

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Calmomusc Liq	Menthyl salicylate (6.3 %) + Eucalyptol (2.1 %) + Levomenthol (3.17 %)	Liquid	Topical	Cardinaux Enrg Les Produits Naturels	1989-12-31	2000-07-07
Dr. Ds Super 7 Pain Relief	Menthyl salicylate (100 mg/1mL) + Menthol (20 mg/1mL)	Cream	Topical	Promedx Innovations Inc	2019-09-04	Not applicable
Extra Strength Hua Tuo Medicated Plaster	Menthyl salicylate (13.84 g/1) + Menthol (3.32 g/1) + Synthetic camphor (8.3 g/1)	Plaster	Topical; Transdermal	Guangzhou Baiyunshan Jingxiutang Pharmaceutical Company	2013-06-17	Not applicable
Flexall Stick	Menthyl salicylate (30 %) + Levomenthol (10 %)	Stick	Topical	Chattem, Inc.	1997-08-07	2003-06-06
Muscle Rub Ultra	Menthyl salicylate (30 g/100g) + Camphor (4 g/100g) + Menthol (10 g/100g)	Cream	Topical	H E B	2011-07-25	Not applicable

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

Menthyl Salicylate, EWG [Link]
Menthyl Salicylate [Link]
Salicylate toxicity [Link]
Best Practice BMJ, Salicylate poisoning [Link]
Salicylate poisoning, patient info [Link]
Medicine.net: menthol and methylsalicylate [Link]
Drug Insert [File]

External Links

ChemSpider: 16736426
RxNav: 1368207
ChEBI: 135976
ZINC: ZINC000000002060

MSDS

Download (52.3 KB)

Clinical Trials

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Phase	Status	Purpose	Conditions	Count	Start Date	Why Stopped	100+ additional columns
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Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Liquid	Topical
Plaster	Topical; Transdermal
Stick	Topical
Patch	Topical
Cream	Topical
Ointment	Topical
Gel	Topical
Patch	Transdermal

Prices

Not Available

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
boiling point (°C)	186	MSDS
logP	4.01	https://www.chemeo.com/cid/67-677-7/Menthyl%20salicylate

Predicted Properties

Property	Value	Source
Water Solubility	0.0275 mg/mL	ALOGPS
logP	4.24	ALOGPS
logP	5.51	Chemaxon
logS	-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	4	Chemaxon
Refractivity	79.25 m³·mol^-1	Chemaxon
Polarizability	31.14 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-00di-7910000000-590d5d6835141226a159
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-000b-9430000000-4b7ab32f35a2a7700e4a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000i-0910000000-a637832f92eab7ef9670
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-000i-2920000000-7e12b4aae0b20a54e360
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00di-3910000000-33ac2f71a7387e665393
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0006-9220000000-c985e8b3bf74bc29d90b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0a4m-9710000000-e2a9c0f2529f357e0fda
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	163.6351	predicted	DeepCCS 1.0 (2019)
[M+H]+	165.9931	predicted	DeepCCS 1.0 (2019)
[M+Na]+	172.8994	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. Prostaglandin G/H synthase 1

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:7947975). Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity)
Specific Function: heme binding
Gene Name: PTGS1
Uniprot ID: P23219
Uniprot Name: Prostaglandin G/H synthase 1
Molecular Weight: 68685.82 Da

References

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]

Details2. Prostaglandin G/H synthase 2

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
Specific Function: enzyme binding
Gene Name: PTGS2
Uniprot ID: P35354
Uniprot Name: Prostaglandin G/H synthase 2
Molecular Weight: 68995.625 Da

References

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 at December 03, 2015 16:51 / Updated at October 21, 2021 04:40

Menthyl salicylate

Identification

Structure for Menthyl salicylate (DB11201)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Clinical Trial & Rare Diseases Add-on Data Package

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References