One systemic acquired resistance signal in tobacco is methyl salicylate. It (0–1 mg/L) possesses the esterase activity of salicylic acid binding protein 2 (SABP2), which is necessary for systemic tissues to perceive SAR signals and changes MeSA into salicylic acid (SA) [2].

Absorption, Distribution and Excretion
Following topical application of methyl salicylate, approximately 12-20% is systemically absorbed through intact skin within 10 hours. Absorption varies depending on factors such as skin surface area and pH. Skin bioavailability ranges from 11.8% to 30.7%. Bioavailability is set at 100% when assessing potential oral exposure to salicylates. Methyl salicylate is primarily excreted via the kidneys as free salicylic acid (10%), salicyluric acid (75%), salicylphenol (10%), acyl glucuronide (5%), and gentic acid (less than 1%). After absorption, methyl salicylate is distributed primarily to most body tissues and extracellular fluids via a pH-dependent passive process. Salicylates are actively transported via a low-volume, saturable transport system and excreted from cerebrospinal fluid via the choroid plexus. The drug readily crosses the placental barrier. It may be rapidly absorbed through intact skin. Intestinal absorption is somewhat unstable…at least partially absorbed as intact esters, and small amounts of carbamates are even excreted by the kidneys in this form…
In human subjects, after oral administration of 7 mg/kg methyl salicylate, the plasma concentration was 1.28 mg% after 0.25 hours and 1.33 mg% after 1.5 hours. /Excerpt from table/
At therapeutic doses, binding is the primary pathway for salicylate elimination, while renal elimination is more important with high doses or multiple administrations. A significant first-pass effect is observed at therapeutic doses. /Salicylate/
Oral salicylates are rapidly absorbed, partially via the stomach, but primarily via the upper small intestine. Significant plasma concentrations are reached in less than 30 minutes; peak concentrations are reached approximately 2 hours after a single dose, then gradually decline. /Salicylate/
For more complete data on the absorption, distribution, and excretion of methyl salicylate (6 types), please visit the HSDB records page.

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Metabolism/Metabolites
A small amount of metabolism may occur in various tissues, but hepatic metabolism is the main pathway for the absorption of methyl salicylate. It is primarily hydrolyzed to salicylic acid by hepatic esterases. Conjugation with glycine forms salicyluric acid, and conjugation with glucuronic acid forms esters or acyl groups, ethers, or phenolic glucuronides; these three are its main metabolites.
…There is evidence that the ester undergoes considerable hydrolysis in the intestine…In some species (e.g., rabbits), a portion may be excreted via free hydroxyl groups in the form of sulfates or glucuronide conjugates. The conjugation reaction appears to occur prior to the hydrolysis of the methyl ester.
At low doses, 80% of hepatic metabolism occurs via conjugation with glycine to form salicyluric acid, and conjugation with glucuronic acid to form salicyl and phenolic glucuronides. The capacity of these two parallel pathways (glycine conjugation, glucuronide conjugation) is limited and easily saturates above therapeutic doses. /Salicylate/
Biotransformation of salicylate occurs in various tissues, particularly in the hepatic endoplasmic reticulum and mitochondria. The three main metabolites are salicyluric acid (a glycine conjugate), ether or phenolic glucuronide, and ester or acyl glucuronide. In addition, small amounts of salicylic acid are oxidized to gentianic acid (2,5-dihydroxybenzoic acid), 2,3-dihydroxybenzoic acid, and 2,3,5-trihydroxybenzoic acid; gentianuric acid, a glycine conjugate of gentianic acid, is also formed. /Salicylate/

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Biological Half-Life
The plasma half-life of low-dose salicylates is 2 to 3 hours, and approximately 12 hours at commonly used anti-inflammatory doses. At high therapeutic doses or in cases of toxicity, the half-life of salicylates can be as long as 15 to 30 hours.
The plasma half-life of low-dose salicylates is 2 to 3 hours, and approximately 12 hours at commonly used anti-inflammatory doses. At high therapeutic doses or in cases of toxicity, the half-life of salicylates can be as long as 15 to 30 hours.

Protein Binding
The degree of albumin binding depends on the plasma concentration of the compound. Interactions Long-term excessive use of analgesic mixtures containing salicylates and acetaminophen or salicylamide can lead to renal papillary necrosis and interstitial nephritis. /Salicylates/ Non-human Toxicity Values Rat oral LD50: 0.887 g/kg Rabbit oral LD50: 2.8 g/kg Guinea pig oral LD50: 1.060 g/kg Dog oral LD50: 2.1 g/kg Guinea pig dermal LD50: 0.70 ml/kg

[1]. A critical review of the literature to conduct a toxicity assessment for oral exposure to methyl salicylate. Crit Rev Toxicol. 2017 Feb;47(2):98-120.

[2]. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance. Science. 2007 Oct 5;318(5847):113-6.

[3]. Fragrance material review on methyl salicylate. Food Chem Toxicol. 2007;45 Suppl 1:S428-52.

[4]. 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.

Methyl salicylate is a colorless, pale yellow, or pale red liquid with a wintergreen odor. (USCG, 1999)
Methyl salicylate is a benzoic acid ester, a methyl ester of salicylic acid. It can be used as a flavoring agent, metabolite, and insect attractant. It is a benzoic acid ester, belonging to the class of salicylates, and is also a methyl ester. It is functionally related to salicylic acid.
Methyl salicylate (wintergreen oil) is an organic ester naturally produced by a variety of plants, particularly those in the genus Ilex. This compound was first extracted and isolated from the plant Gaultheria procumbens in 1843. It can be synthesized artificially and used as a flavoring agent in food, beverages, and liniments. It forms a colorless to pale yellow or pale red liquid with the characteristic odor and taste of wintergreen. Methyl salicylate can be used as a reddening agent and analgesic in deep heat compresses for the treatment of acute joint and muscle pain. It is used in small concentrations as a flavoring agent in chewing gum and mints, and added as a preservative in mouthwash solutions. Methyl salicylate has been reported to be found in tea trees (Camellia sinensis), European cork mushrooms (Phellinus tremulae), and several other organisms with relevant data. Methyl 2-hydroxybenzoate is present in beverages. It is found in white wine, tea, Boletus edulis, Bourbon vanilla, clary sage, red sage, and fruits such as cherries, apples, raspberries, papayas, and plums. Methyl 2-hydroxybenzoate is also found in the leaves of holly (Gaultheria procumbens). Methyl 2-hydroxybenzoate is a flavoring agent. Methyl 2-hydroxybenzoate is a metabolite of the yeast Saccharomyces cerevisiae. See also: Salicylic acid (active component); clove oil (one of the ingredients); levamperitone; methyl salicylate (one of the ingredients)... See more...

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Drug Indications
Topical ointments or liniments containing methyl salicylate are used as counterstimulants to relieve acute pain in the lower back, sciatica, and rheumatic diseases. Suitable for use as a topical analgesic in humans and veterinarians.

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Mechanism of Action
Counterstimulation is thought to be effective in relieving musculoskeletal pain because stimulation of sensory nerve endings is thought to alter or counteract pain in muscles or joints innervated by the same nerve. This is believed to mask underlying musculoskeletal pain and discomfort. When applied topically, methyl salicylate is thought to penetrate the skin and subcutaneous tissue, where it reversibly inhibits cyclooxygenase and prevents the production of inflammatory mediators such as prostaglandins and thromboxane A2 both locally and peripherally.

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Therapeutic Uses
Ointments or liniments containing methyl salicylate can be used topically as a stimulant to relieve back pain, sciatica, and pain caused by rheumatic diseases. Previously used in small doses as a carminative.
Medication (Veterinary): Oral administration, primarily as a flavoring agent or carminative; topically, as a stimulant or stimulant, used in conjunction with massage or rubbing, for example, in breast ointments (concentration 1-3%), ointments, and mixtures of stimulants and stimulants (at least 5-10%), applied to painful joints, muscles, and bones.
Topical analgesia for humans and veterinarians.

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Drug Warnings
Ointments or liniments…should not be applied to burns or other damaged skin…usually at concentrations of 10-25%….
Methyl salicylate can be absorbed through the skin; misuse of this drug topically can lead to systemic poisoning and even death. It is a common pediatric poison and its use should be strongly prohibited. Children with fever and dehydration are particularly susceptible to poisoning from relatively small doses of salicylates. …Aspirin is contraindicated in children and adolescents with febrile viral illnesses due to the risk of Reye's syndrome. /Salicylate/

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Pharmacodynamics
Methyl salicylate relieves musculoskeletal pain in muscles, joints, and tendons by causing skin redness and irritation through vasodilation and increased blood flow. Its pharmacological action is similar to that of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), but as a topical medication, it primarily acts as an erythematous and skin irritant. This counter-irritant effect is thought to provide a soothing warming sensation.

C8H8O3

152.14

152.047

119-36-8

Methyl Salicylate-d4;1219802-12-6

4133

Colorless to light yellow liquid

1.2±0.1 g/cm3

222.0±0.0 °C at 760 mmHg

-8 °C

86.8±12.6 °C

0.1±0.4 mmHg at 25°C

1.547

2.23

1

3

2

11

144

0

O(C([H])([H])[H])C(C1=C([H])C([H])=C([H])C([H])=C1O[H])=O

OSWPMRLSEDHDFF-UHFFFAOYSA-N

InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3

methyl 2-hydroxybenzoate

Gaultheria oil; Betula; Methyl salicylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Ethanol : ~25 mg/mL (~164.31 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.43 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (16.43 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)