Trolamine salicylate

Identification

Summary

Trolamine salicylate is a medication used to relieve minor aches and pains of the muscles and joints.

Brand Names
Asper-flex, Aspercreme, Mobisyl, Myoflex, Sportscreme
Generic Name
Trolamine salicylate
DrugBank Accession Number
DB11079
Background

Trolamine salicylate is an organic compound or a salt formed between triethanolamine and salicylic acid. Triethanolamine neutralizes the acidity of the salicylic acid. It is a topical analgesic used for temporary relief of minor pain associated with arthritis, simple backache, muscle strains, sprains, and bruises. Unlike other topical analgesics, trolamine salicylate has no distinct odor which improves patient acceptability 2. It also displays low systemic absorption upon dermal or topical administration 3 and has low skin irritant properties 4. As with other salicylates, trolamine salicylate is an inhibitor of cyclo-oxygenase (COX) enzymes with no reported selectivity towards a specific enzyme isoform. Trolamine salicylate serves as an active ingredient in topical over-the-counter products for temporary management of mild to moderate muscular and joint pains.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 287.312
Monoisotopic: 287.1368874
Chemical Formula
C13H21NO6
Synonyms
  • Trolamine salicylate

Pharmacology

Indication

Indicated for the temporary relief of aches, and pains of muscles and joints associated with backache, lumbago, strains, bruises, sprains and arthritic or rheumatic pain, pain of tendons and ligaments 6.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Trolamine salicylate is a salicylate that inhibits cyclo-oxygenase (COX) enzymes responsible for generating pro-inflammatory factors such as to induce pain and inflammation. It is thought to mediate its analgesic effect through inhibition of COX-2 enzyme, which is an induced enzyme responsible for inflammatory responses and pain in muscle and joint disorders. By inhibiting fatty acid COX enzyme, trolamine salicylate inhibits the production of prostaglandins and thromboxanes in inflammatory cells involved in generating pain and inflammation 5. It thereby works to temporarily reduce mild to moderate pain. In subjects with muscle soreness from exercise, administration of topical trolamine salicylate was associated with reduced duration and severity of muscule soreness compared to placebo 2. In subjects with osteoarthritis in hands, trolamine salicylate cream was shown to be effective in achieving temporary relief of minor pain and stiffness 1.

Mechanism of action

Inflammation and tissue damage in different conditions including arthritis, bursitis, joint disorder, bruises, and strains or sprains of muscle origin, induce mild to moderate pain and are associated with increase prostaglandin synthesis 5. This is thought to be a result of COX-2 enzyme induction. COX-2 is induced in inflammatory cells in case of cell injury, infection or activation from inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor (TNF)-α. Upon activation, COX-2 produces prostanoid mediators of inflammation such as prostaglandins and thromboxanes 5. Trolamine salicylate mediates its analgesic effect by inhibiting the production of inflammatory mediators that sensitize nociceptive nerve endings and generate pain 5.

TargetActionsOrganism
AProstaglandin G/H synthase 1
inhibitor
Humans
AProstaglandin G/H synthase 2
inhibitor
Humans
Absorption

Following topical administration of 10% trolamine salicylate in healthy volunteers, salicylic acid could not be detected in serum indicating low systemic absorption 3.

Volume of distribution

Topical administration of 1 gram of 10% trolamine salicylate in abdominal rat skin resulted in an approximate extravascular volume of distribution (V/F) of 24.0 mL 4.

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Following topical administration of 10% trolamine salicylate in healthy volunteers, urinary recovery of total salicylate during the first 24 hours was 6.9 mg (p < 0.05), which is 1.4% of total dose 3.

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

It is hazardous in case of ingestion MSDS. The carcinogenicity, mutagenicity and effects on reproductive fertility of trolamine salicylate have not been reported.

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.
DrugInteraction
AbciximabThe risk or severity of bleeding can be increased when Trolamine salicylate is combined with Abciximab.
AcarboseTrolamine salicylate may increase the hypoglycemic activities of Acarbose.
AceclofenacThe therapeutic efficacy of Trolamine salicylate can be decreased when used in combination with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Trolamine salicylate is combined with Acemetacin.
AcenocoumarolTrolamine salicylate may increase the anticoagulant activities of Acenocoumarol.
Food Interactions
No interactions found.

Products

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Active Moieties
NameKindUNIICASInChI Key
Salicylic acidsaltO414PZ4LPZ69-72-7YGSDEFSMJLZEOE-UHFFFAOYSA-N
Trolaminesalt9O3K93S3TK102-71-6GSEJCLTVZPLZKY-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Abr 90Spray10 g/100mLTopicalABR Medical, Inc.2000-11-012014-06-04US flag
Abr 90Spray10 g/100mLTopicalNorthwest Cosmetic Laboratories2000-11-012010-06-01US flag
Actiflex Pain Relief RubCream10 %TopicalPendopharm Division Of Pharmascience Inc2003-01-202011-09-30Canada flag
Alcis Daily Relief Pain ReliefCream10 g/100mLTopicalAlcis Topical, Inc.2009-03-09Not applicableUS flag
Alcis Topical Pain Relief CreamCream10 % w/wTopicalAlcis Health Inc.Not applicableNot applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Arthritis Extra Strength Roll-ON LotionTrolamine salicylate (10 % w/w) + Capsaicin (0.035 % w/w) + Levomenthol (1.25 % w/w)LotionTopicalChurch & Dwight Canada Corp2008-09-152019-10-23Canada flag
Arthritis Pain ReliefTrolamine salicylate (10 % w/w) + Capsaicin (0.035 % w/w) + Levomenthol (1.25 % w/w)LotionTopicalChurch & Dwight Canada Corp2019-10-28Not applicableCanada flag
Arthur Itis CreamTrolamine salicylate (10 %) + Capsaicin (0.025 %)CreamTopicalNabtech Pharma Inc.1997-09-262005-09-20Canada flag
Ease Pain Away Analgesic LotionTrolamine salicylate (10 %) + Levomenthol (1.25 %)LotionTopicalRmc Group Inc.1994-12-311999-11-23Canada flag
ELF Flawless Finish Foundation SPF 15 Oil FreeTrolamine salicylate (2 g/100g) + Titanium dioxide (5.5 g/100g)CreamTopicalJ. A. Cosmetics U.S. INC2011-10-032017-12-31US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Permavan External PatchTrolamine salicylate (10 g/100g) + Dextromethorphan hydrobromide monohydrate (4 g/100g) + Lidocaine (4 g/100g)PatchTopicalHome Aide Diganostics, Inc.2015-03-09Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 1,2-aminoalcohols. These are organic compounds containing an alkyl chain with an amine group bound to the C1 atom and an alcohol group bound to the C2 atom.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
1,2-aminoalcohols
Alternative Parents
Trialkylamines / Monocarboxylic acids and derivatives / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
1,2-aminoalcohol / Alcohol / Aromatic homomonocyclic compound / Hydrocarbon derivative / Monocarboxylic acid or derivatives / Organic oxygen compound / Organooxygen compound / Organopnictogen compound / Primary alcohol / Tertiary aliphatic amine
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
H8O4040BHD
CAS number
2174-16-5
InChI Key
UEVAMYPIMMOEFW-UHFFFAOYSA-N
InChI
InChI=1S/C7H6O3.C6H15NO3/c8-6-4-2-1-3-5(6)7(9)10;8-4-1-7(2-5-9)3-6-10/h1-4,8H,(H,9,10);8-10H,1-6H2
IUPAC Name
2-[bis(2-hydroxyethyl)amino]ethan-1-ol; 2-hydroxybenzoic acid
SMILES
OCCN(CCO)CCO.OC(=O)C1=CC=CC=C1O

References

General References
  1. Rothacker DQ, Lee I, Littlejohn TW 3rd: Effectiveness of a single topical application of 10|x% trolamine salicylate cream in the symptomatic treatment of osteoarthritis. J Clin Rheumatol. 1998 Feb;4(1):6-12. [Article]
  2. Hill DW, Richardson JD: Effectiveness of 10% trolamine salicylate cream on muscular soreness induced by a reproducible program of weight training. J Orthop Sports Phys Ther. 1989;11(1):19-23. [Article]
  3. Morra P, Bartle WR, Walker SE, Lee SN, Bowles SK, Reeves RA: Serum concentrations of salicylic acid following topically applied salicylate derivatives. Ann Pharmacother. 1996 Sep;30(9):935-40. doi: 10.1177/106002809603000903. [Article]
  4. Sajjadi P, Khodayar MJ, Sharif Makhmalzadeh B, Rezaee S: Percutaneous absorption of salicylic Acid after administration of trolamine salicylate cream in rats with transcutol((R)) and eucalyptus oil pre-treated skin. Adv Pharm Bull. 2013;3(2):295-301. doi: 10.5681/apb.2013.048. Epub 2013 Aug 20. [Article]
  5. 26. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 318-322). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  6. Health Canada: Triethanolamine Salicylate (Trolamine) Label [Link]
PubChem Compound
25213
PubChem Substance
347827887
ChemSpider
23549
RxNav
38866
ChEMBL
CHEMBL2107288
Wikipedia
Trolamine_salicylate
MSDS
Download (47.5 KB)

Clinical Trials

Clinical Trials
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
2TerminatedTreatmentCutaneous Mastocytoses1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CreamTopical10 g/100mL
OintmentTopical13.3 %
CreamTopical10 g/100g
LotionTopical10 %
SprayTopical100 mg/1mL
SprayTopical0.1 g/100mL
CreamTopical10 % w/w
CreamTopical15 % / g
CreamTopical0.1 g/1g
Aerosol, foamTopical0.1 g/1g
LiquidTopical10 g/100g
GelTopical15 %
CreamTopical100 mg/1mL
LotionTopical10 g/100g
Aerosol, foamTopical10 mg/100mL
LotionTopical
LotionTopical10.0 %
CreamTopical
CreamTopical15 %
CreamTopical15 % w/w
SprayTopical10 g/100mL
Cream; kit; tablet, delayed releaseOral; Topical
GelTopical10 g/100mL
CreamTopical10 mg/1g
PatchTopical12.5 %
GelTopical
CreamCutaneous10 g/1
CreamTopical20 %
CreamTopical13.3 %
PatchTopical
LotionTopical10 g/100mL
CreamTopical13.3 % w/w
CreamTopical10 %
GelTopical10 g/100g
GelTopical10 % w/w
CreamTopical20 % w/w
SalveTopical100 mg/1g
GelTopical100 mg/1mL
GelTopical100 mg/1g
CreamTopical8.5 g/85g
CreamTopical100 mg/1g
LiquidTopical100 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
PropertyValueSource
melting point (°C)50MSDS
boiling point (°C)DecomposesMSDS
water solubilitySolubleMSDS
Predicted Properties
PropertyValueSource
Water Solubility11.3 mg/mLALOGPS
logP1.96ALOGPS
logP1.98Chemaxon
logS-1.1ALOGPS
pKa (Strongest Acidic)2.79Chemaxon
pKa (Strongest Basic)-6.3Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area57.53 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity35.3 m3·mol-1Chemaxon
Polarizability12.82 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-158.79921
predicted
DeepCCS 1.0 (2019)
[M+H]+161.15721
predicted
DeepCCS 1.0 (2019)
[M+Na]+167.29376
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
  1. Topical Analgesic and Anesthetic Agents Drug Class Review [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
  1. Topical Analgesic and Anesthetic Agents Drug Class Review [Link]

Drug created at December 03, 2015 16:51 / Updated at October 09, 2024 08:18