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Chemistry

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Also known as: Methyl 2-hydroxybenzoate, 119-36-8, Wintergreen oil, Gaultheria oil, Betula oil, Sweet birch oil
Molecular Formula
C8H8O3
Molecular Weight
152.15  g/mol
InChI Key
OSWPMRLSEDHDFF-UHFFFAOYSA-N
FDA UNII
LAV5U5022Y

Methyl Salicylate
Methyl 2-hydroxy benzoate is a metabolite found in or produced by Saccharomyces cerevisiae.
1 2D Structure

Methyl Salicylate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
methyl 2-hydroxybenzoate
2.1.2 InChI
InChI=1S/C8H8O3/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5,9H,1H3
2.1.3 InChI Key
OSWPMRLSEDHDFF-UHFFFAOYSA-N
2.1.4 Canonical SMILES
COC(=O)C1=CC=CC=C1O
2.2 Other Identifiers
2.2.1 UNII
LAV5U5022Y
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Hewedolor

2. Linsal

3. Methyl Salicylate Sodium Salt

4. Methylsalicylate

5. Metsal Liniment

6. Rheumabal

2.3.2 Depositor-Supplied Synonyms

1. Methyl 2-hydroxybenzoate

2. 119-36-8

3. Wintergreen Oil

4. Gaultheria Oil

5. Betula Oil

6. Sweet Birch Oil

7. Teaberry Oil

8. Oil Of Wintergreen

9. Analgit

10. 2-hydroxybenzoic Acid Methyl Ester

11. Spicewood Oil

12. 2-carbomethoxyphenol

13. Gaultheriaoel

14. Wintergruenoel

15. Flucarmit

16. Betula

17. Exagien

18. Natural Wintergreen Oil

19. Methyl O-hydroxybenzoate

20. 2-(methoxycarbonyl)phenol

21. Methylsalicylate

22. Betula Lenta

23. Salicylic Acid, Methyl Ester

24. Benzoic Acid, 2-hydroxy-, Methyl Ester

25. Synthetic Wintergreen Oil

26. Gaultheria Oil, Artificial

27. Wintergreen Oil, Synthetic

28. Methyl2-hydroxybenzoate

29. O-hydroxybenzoic Acid, Methyl Ester

30. Fema No. 2745

31. Birch Oil, Sweet

32. Salicylic Acid Methyl Ester

33. Mfcd00002214

34. 68917-75-9

35. Flavor,wintergreen

36. Nsc 8204

37. 2-hydroxybenzoic Acid, Methyl Ester

38. Metylester Kyseliny Salicylove

39. Fema No. 2154

40. Fema No. 3113

41. Nsc-8204

42. 2-hydroxy-benzoic Acid Methyl Ester

43. Benzoic Acid, Hydroxy-, Methyl Ester

44. Methyl Salicylate,synthetic

45. Lav5u5022y

46. Chebi:31832

47. 135952-76-0

48. Ncgc00091106-02

49. Dsstox_cid_5659

50. Dsstox_rid_77872

51. Dsstox_gsid_25659

52. Caswell No. 577

53. Panalgesic

54. Theragesic

55. 2,4-cyclohexadien-1-one,6-(hydroxymethoxymethylene)-(9ci)

56. Predalure

57. Fema Number 2745

58. Black Birch Oil

59. Methyl Salicylate [jan]

60. Anthrapole Nd

61. Betula Lenta Oil

62. Ben Gay

63. Methyl Salicylate (natural)

64. 68917-50-0

65. Cas-119-36-8

66. Ccris 6259

67. Hsdb 1935

68. Winter Green Oil

69. Einecs 204-317-7

70. Epa Pesticide Chemical Code 076601

71. Metylester Kyseliny Salicylove [czech]

72. Methylester Kyseliny Salicylove [czech]

73. Brn 0971516

74. Unii-lav5u5022y

75. Wintergreen

76. Methyl Salicylate [jan:nf]

77. Methylester Kyseliny Salicylove

78. Ai3-00090

79. Methyl-salicylate

80. Salicylic Acid Methyl

81. 1-o-methylsalicylate

82. Salonpas (salt/mix)

83. Salicylate Methyl Ester

84. Birch Oil Sweet

85. Methyl Salicylate,(s)

86. Theragesic (salt/mix)

87. Methyl Salicylate (tn)

88. Methyl Salicylate, 8ci

89. Methyl-2-hydroxybenzoate

90. Enamine_001611

91. Teaberry Leaf Oil

92. Methyl Salicylate, 98%

93. Birch, Sweet, Oil

94. Methyl Salicylate, Bioxtra

95. Salicylic-acid Methyl Ester

96. Wln: Qr Bvo1

97. Ec 204-317-7

98. Wintergreen [vandf]

99. Wintergreen Leaf Oil

100. Schembl5312

101. Betula Oil, Wintergreen Oil

102. Checkerberry Leaf Oil

103. Sweet Birch Bark Oil

104. Betula Lenta Bark Oil

105. Cherry Birch Bark Oil

106. Mountain-tea Leaf Oil

107. Zinc490

108. 4-10-00-00143 (beilstein Handbook Reference)

109. 90045-28-6

110. Bidd:er0323

111. Wintergreen Oil [fcc]

112. Wintergreen Oil, China Origin

113. Methyl Salicylate [ii]

114. Methyl Salicylate [mi]

115. Wintergreen Oil [fhfi]

116. Chembl108545

117. Gtpl2431

118. Methyl Salicylate (jp17/nf)

119. Birch Sweet Oil [fhfi]

120. Methyl Salicylate [fcc]

121. Dtxsid5025659

122. Methyl Salicylate [fhfi]

123. Methyl Salicylate [hsdb]

124. Methyl Salicylate [inci]

125. Sweet Birch Oil [vandf]

126. Eastern Teaberry Leaf Oil

127. Fema 2745

128. Methyl Salicylate [vandf]

129. Nsc8204

130. Methyl Salicylate [mart.]

131. Hms1398j05

132. Hms2089h12

133. Hms3885c04

134. O-hydroxybenzoic Acid Methyl Ester

135. Methyl Salicylate [usp-rs]

136. Methyl Salicylate [who-dd]

137. Bcp29151

138. Cs-b1799

139. Hy-y0189

140. Methyl Ester 2-hydroxy-benzoic Acid

141. Tox21_111081

142. Tox21_201543

143. Tox21_300137

144. Bbl010504

145. S3756

146. Stk397388

147. Betula Lenta Bark Oil [inci]

148. Gaultheria Procumbens Leaf Oil

149. Methyl Salicylate, Analytical Standard

150. Akos000118977

151. Ccg-266225

152. Db09543

153. Methyl Ester Of 2-hydroxy-benzoic Acid

154. Methyl Salicylate [ep Impurity]

155. Methyl Salicylate [orange Book]

156. Methyl Salicylate [ep Monograph]

157. Methyl Salicylate, >=98%, Fcc, Fg

158. Ncgc00091106-01

159. Ncgc00091106-03

160. Ncgc00091106-04

161. Ncgc00091106-05

162. Ncgc00254104-01

163. Ncgc00259093-01

164. 8024-54-2

165. Ac-11584

166. Sy008800

167. Ts-02010

168. Methyl Salicylate,synthetic [vandf]

169. Salonpas Component Methyl Salicylate

170. Db-012808

171. Ft-0612582

172. Ft-0622968

173. Ft-0695782

174. Ft-0698844

175. Methyl Salicylate, Natural, 98%, Fcc, Fg

176. Methyl Salicylate Component Of Salonpas

177. Methyl Salicylate, Puriss., 99.0-100.5%

178. D01087

179. D70335

180. Methyl Salicylate, Saj First Grade, >=98.0%

181. Methyl Salicylate, Tested According To Ph.eur.

182. Ab01275470-01

183. Methyl Salicylate 100 Microg/ml In Acetonitrile

184. A804265

185. Methyl Salicylate, Reagentplus(r), >=99% (gc)

186. Methyl Salicylate, Vetec(tm) Reagent Grade, 99%

187. Q407669

188. Sr-05000001473

189. Gaultheria Procumbens (wintergreen) Leaf Oil

190. Q-100939

191. Sr-05000001473-1

192. Z19703590

193. 2-[hydroxy(methoxy)methylene]-3,5-cyclohexadiene-1-one

194. F0001-0306

195. 6-[(e)-methoxyhydroxymethylene]-2,4-cyclohexadiene-1-one

196. Gaultheria Procumbens (wintergreen) Leaf Oil [inci]

197. Methyl Salicylate, United States Pharmacopeia (usp) Reference Standard

198. Methyl Salicylate, Pharmaceutical Secondary Standard; Certified Reference Material

199. 9041-28-5

200. Gaultheria Oil Pound>>wintergreen Oil Pound>>2-hydroxy-benzoicacimethylester Pound>>methyl 2-hydroxybenzoate

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 152.15 g/mol
Molecular Formula C8H8O3
XLogP32.3
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count3
Rotatable Bond Count2
Exact Mass152.047344113 g/mol
Monoisotopic Mass152.047344113 g/mol
Topological Polar Surface Area46.5 Ų
Heavy Atom Count11
Formal Charge0
Complexity144
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

OINTMENTS OR LINIMENTS CONTAINING METHYL SALICYLATE ARE APPLIED TOPICALLY AS COUNTERIRRITANTS FOR RELIEF OF PAIN ASSOCIATED WITH LUMBAGO, SCIATICA, AND RHEUMATIC CONDITIONS. FORMERLY USED INTERNALLY IN SMALL DOSES AS A CARMINATIVE.

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 84:2404


MEDICATION (VET): ORALLY, PRIMARILY AS FLAVORING AGENT OR AS CARMINATIVE; TOPICALLY, AS IRRITANT OR COUNTERIRRITANT AIDED BY MASSAGE OR RUBBING AS IN UDDER OINTMENTS (1-3% CONCN), POULTICES & COUNTERIRRITANT MIXT (@ LEAST 5-10%) OVER SORE JOINT, MUSCLE, & BONE AREAS.

Rossoff, I.S. Handbook of Veterinary Drugs. New York: Springer Publishing Company, 1974., p. 360


LOCAL ANALGESIC FOR HUMAN AND VETERINARY MEDICINE

SRI


4.2 Drug Warning

OINTMENTS OR LINIMENTS ... . SHOULD NOT BE APPLIED TO BURNED AREAS OR TO OTHERWISE DAMAGED SKIN...USUALLY IN CONCN FROM 10-25% ... .

American Hospital Formulary Service. Volumes I and II. Washington, DC: American Society of Hospital Pharmacists, to 1984., p. 84:2404


ABSORPTION OF METHYL SALICYLATE CAN OCCUR THROUGH THE SKIN, & DEATH HAS RESULTED FROM SYSTEMIC POISONING FROM THE LOCAL MISAPPLICATION OF THE DRUG. IT IS A COMMON PEDIATRIC POISON, & ITS USE SHOULD BE STRONGLY DISCOURAGED.

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 653


Children with fever and dehydration are particularly prone to intoxication from relatively small doses of salicylate. ... The use of aspirin is contraindicated in children and adolescents with febrile viral illnesses because of the risk of Reye's syndrome. /Salicylates/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 651


4.3 Minimum/Potential Fatal Human Dose

4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) 50-500 MG/KG, BETWEEN 1 TEASPOON &1 OZ FOR 70 KG PERSON (150 LB).

Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-205


4.4 Drug 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.


5 Pharmacology and Biochemistry
5.1 Pharmacology

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.


5.2 MeSH Pharmacological Classification

Antirheumatic Agents

Drugs that are used to treat RHEUMATOID ARTHRITIS. (See all compounds classified as Antirheumatic Agents.)


Fixatives

Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. (See all compounds classified as Fixatives.)


5.3 Absorption, Distribution and Excretion

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%.


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%).


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.


MAY BE ABSORBED RAPIDLY THROUGH INTACT SKIN. BOWEL ABSORPTION IS SOMEWHAT ERRATIC ... ABSORBED AT LEAST IN PART AS THE INTACT ESTER AND SMALL AMT ARE EVEN EXCRETED AS SUCH BY THE KIDNEYS ... .

Gosselin, R.E., R.P. Smith, H.C. Hodge. Clinical Toxicology of Commercial Products. 5th ed. Baltimore: Williams and Wilkins, 1984., p. II-205


HUMAN SUBJECTS WERE GIVEN 7 MG/KG OF METHYL SALICYLATE BY MOUTH. AFTER 0.25 HOURS THE BLOOD CONCN WAS 1.28 MG%. AFTER 1.5 HOURS THE BLOOD CONCN WAS 1.33 MG%. /FROM TABLE/

Sunshine, I. (ed.). CRC Handbook of Analytical Toxicology. Cleveland: The Chemical Rubber Co., 1969., p. 362


At therapeutic doses, conjugation accounts for most salicylic elimination, whereas renal elimination becomes more important with large or multiple doses. A substantial first-pass effect occurs at therapeutic doses. /Salicylates/

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 563


Orally ingested salicylates are absorbed rapidly, partly from the stomach but mostly from the upper small intestine. Appreciable conc are found in plasma in less than 30 min; after a single dose, a peak value is reached in about 2 hr and then gradually declines. /Salicylates/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 649


For more Absorption, Distribution and Excretion (Complete) data for METHYL SALICYLATE (6 total), please visit the HSDB record page.


5.4 Metabolism/Metabolites

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.


...EVIDENCE THAT CONSIDERABLE HYDROLYSIS OF ESTER OCCURS IN INTESTINAL TRACT... IN SOME SPECIES, SUCH AS RABBIT, MAY BE PARTLY EXCRETED AS SULFATE OR GLUCURONIC ACID CONJUGATE ON THE FREE HYDROXYL GROUP. CONJUGATION APPEARS TO TAKE PLACE BEFORE HYDROLYSIS OF THE METHYL ESTER.

Patty, F. (ed.). Industrial Hygiene and Toxicology: Volume II: Toxicology. 2nd ed. New York: Interscience Publishers, 1963., p. 1899


For small doses 80% of the hepatic metabolism results from conjugation with glycine to form salicyluric acid and with glucuronic acid to form salicyl acyl and phenolic glucuronide. The two parallel pathways (glycine, glucuronide conjugation) have limited capacity and saturate easily above therapeutic doses. /Salicylates/

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 563


The biotransformation of salicylates takes place in many tissues, but particularly in the hepatic endoplasmic reticulum and mitochondria. The three chief metabolic products are salicyluric acid (the glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. In addition, a small fraction is oxidized to gentisic acid (2,5-dihydroxybenzoic acid) and to 2,3-dihydroxybenzoic and 2,3,5-trihydroxybenzoic acids; gentisuric acid, the glycine conjugate of gentisic acid, is also formed. /Salicylates/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 649


5.5 Biological 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.


The plasma half-life for ... salicylate is 2 to 3 hr in low doses and about 12 hr at usual antiinflammatory doses. The half-life of salicylate may be as long as 15 to 30 hr at high therapeutic doses or when there is intoxication. /Salicylates/

Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 650


5.6 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. 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.


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02-Jan-2021
31-Aug-2024
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