Trolamine salicylate

Identification

Name
Trolamine salicylate
Accession Number
DB11079
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
Not Available
Active Moieties
NameKindUNIICASInChI Key
Salicylic acidsaltO414PZ4LPZ69-72-7YGSDEFSMJLZEOE-UHFFFAOYSA-N
Trolaminesalt9O3K93S3TK102-71-6GSEJCLTVZPLZKY-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Abr 90Spray10 g/100mLTopicalABR Medical, Inc.2000-11-012014-06-04Us
Abr 90Spray10 g/100mLTopicalNorthwest Cosmetic Laboratories LLC2000-11-012010-06-01Us
Actiflex Pain Relief RubCream10 %TopicalPendopharm Division Of De Pharmascience Inc2003-01-202011-09-30Canada
Alcis Daily Relief Pain ReliefCream10 g/100mLTopicalAlcis Topical, Inc.2009-03-09Not applicableUs
Alcis Topical Pain Relief CreamCream10 %TopicalAlcis Health Inc.Not applicableNot applicableCanada
AnalgesicCream10 g/100gTopicalMeijer Distribution1990-04-152012-11-12Us
Analgesic CreamCream15 %TopicalPharmascience Inc2013-10-08Not applicableCanada
Analgesic Creme RubCream100 mg/1gTopicalMajor2014-05-10Not applicableUs
Antiphlogistine Rub A-535 No Odour Fmla OntOintment13.3 %TopicalCarter Products, Division Of Carter Wallace Ns Inc.1993-12-311997-08-14Canada
ArthricreamCream10 g/100gTopicalKroger1992-02-04Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Arthur Itis CreamTrolamine salicylate (10 %) + Capsaicin (0.025 %)CreamTopicalNabtech Pharma Inc.1997-09-262005-09-20Canada
ELF Flawless Finish Foundation SPF 15 Oil FreeTrolamine salicylate (2 g/100g) + Titanium dioxide (5.5 g/100g)CreamTopicalJ. A. Cosmetics U.S. INC2011-10-03Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
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
Categories
UNII
H8O4040BHD
CAS number
2174-16-5
Weight
Average: 287.312
Monoisotopic: 287.1368874
Chemical Formula
C13H21NO6
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

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].

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
Human
AProstaglandin G/H synthase 2
inhibitor
Human
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
Toxicity

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

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Trolamine salicylate is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Trolamine salicylate is combined with (S)-Warfarin.
2,4-thiazolidinedioneTrolamine salicylate may increase the hypoglycemic activities of 2,4-thiazolidinedione.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Trolamine salicylate is combined with 4-hydroxycoumarin.
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 risk or severity of adverse effects can be increased when Aceclofenac is combined with Trolamine salicylate.
AcemetacinThe risk or severity of adverse effects can be increased when Acemetacin is combined with Trolamine salicylate.
AcenocoumarolThe risk or severity of bleeding can be increased when Trolamine salicylate is combined with Acenocoumarol.
AcetohexamideTrolamine salicylate may increase the hypoglycemic activities of Acetohexamide.
Food Interactions
Not Available

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. [PubMed:19078236]
  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. [PubMed:18796932]
  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. [PubMed:8876850]
  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. [PubMed:24312851]
  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]
External Links
PubChem Compound
25213
PubChem Substance
347827887
ChemSpider
23549
ChEMBL
CHEMBL2107288
Wikipedia
Trolamine_salicylate
AHFS Codes
  • 28:08.04.24 — Salicylates
MSDS
Download (47.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentMinor burns1
2TerminatedTreatmentToothache1
3CompletedTreatmentNon-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentPain, Neuropathic1
4CompletedTreatmentCaudal epidural block therapy / Forearm Injuries / Orthopedic Procedures / Traumas / Upper Extremity1
4CompletedTreatmentCaudal epidural block therapy / Orthopedic Procedures / Shoulder1
Not AvailableCompletedTreatmentCerebral Palsy (CP)1
Not AvailableCompletedTreatmentErectile Dysfunction (ED)1
Not AvailableCompletedTreatmentRecession, Gingival1
Not AvailableRecruitingBasic ScienceHeart Failure, Unspecified1
Not AvailableRecruitingTreatmentCervical Osteoarthritis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical10 g/100mL
CreamTopical100 mg/1g
OintmentTopical13.3 %
CreamTopical10 g/100g
LotionTopical10 %
SprayTopical100 mg/1mL
SprayTopical0.1 g/100mL
CreamTopical
LiquidTopical10 g/100g
GelTopical15 %
LotionTopical10.0 %
CreamTopical13.3 %
CreamTopical15 %
SprayTopical10 g/100mL
PatchTopical12.5 %
CreamCutaneous10 g/1
CreamTopical20 %
PatchTopical
CreamTopical10 %
LotionTopical10 g/100mL
CreamTopical8.5 g/85g
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 MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Tertiary aliphatic amine / Tertiary amine / 1,2-aminoalcohol / Monocarboxylic acid or derivatives / Organic oxygen compound / Organopnictogen compound / Hydrocarbon derivative / Primary alcohol / Organooxygen compound / Alcohol
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
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
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
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 on December 03, 2015 09:51 / Updated on December 16, 2018 23:30