Choline magnesium trisalicylate

Identification

Name
Choline magnesium trisalicylate
Accession Number
DB01401
Type
Small Molecule
Groups
Approved
Description

Choline magnesium trisalicylate is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. Trisalicylate significantly reduces methotrexate renal clearance, displacing methotrexate from protein, increasing the fraction unbound by 28% [1, 2].

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Tricosal / Trilisate
Categories
UNII
DJJ95FJP1H
CAS number
64425-90-7
Weight
Average: 539.814
Monoisotopic: 539.164188051
Chemical Formula
C26H29MgNO10
InChI Key
FQCQGOZEWWPOKI-UHFFFAOYSA-K
InChI
InChI=1S/3C7H6O3.C5H14NO.Mg/c3*8-6-4-2-1-3-5(6)7(9)10;1-6(2,3)4-5-7;/h3*1-4,8H,(H,9,10);7H,4-5H2,1-3H3;/q;;;+1;+2/p-3
IUPAC Name
magnesium(2+) ion (2-hydroxyethyl)trimethylazanium tris(2-hydroxybenzoate)
SMILES
[Mg++].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O

Pharmacology

Indication

Choline magnesium trisalicylate is used to reduce pain and inflammation caused by conditions such as arthritis. This medication is also used to treat fever in adults.

Associated Conditions
Pharmacodynamics

Trisalicylate-choline is a non-steroidal anti-inflammatory drug (NSAID) that contains a combination of choline salicylate and magnesium salicylate. Does not affect platelet aggregation.

Mechanism of action

Inhibits prostaglandin synthesis; acts on the hypothalamus heat-regulating center to reduce fever; blocks the generation of pain impulses

TargetActionsOrganism
UProstaglandin G/H synthase 1
inhibitor
Human
UProstaglandin G/H synthase 2
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

renal

Half life
Not Available
Clearance
Not Available
Toxicity

Salicylate intoxication, known as salicylism, may occur with large doses or extended therapy. Common symptoms of salicylism include headache, dizziness, tinnitus, hearing impairment, confusion, drowsiness, sweating, vomiting, diarrhea, and hyperventilation. A more severe degree of salicylate intoxication can lead to CNS disturbances, alteration in electrolyte balance, respiratory and metabolic acidosis, hyperthermia, and dehydration.

Affected organisms
Not Available
Pathways
PathwayCategory
Trisalicylate-Choline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Choline magnesium trisalicylate.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Choline magnesium trisalicylate is combined with Abciximab.
AcebutololCholine magnesium trisalicylate may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Choline magnesium trisalicylate is combined with Acemetacin.
AcenocoumarolCholine magnesium trisalicylate may increase the anticoagulant activities of Acenocoumarol.
AcetaminophenCholine magnesium trisalicylate may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Nadkarni MM, Peller CA, Retig J: Eosinophilic hepatitis after ingestion of choline magnesium trisalicylate. Am J Gastroenterol. 1992 Jan;87(1):151-3. [PubMed:1728115]
  2. Tracy TS, Krohn K, Jones DR, Bradley JD, Hall SD, Brater DC: The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis. Eur J Clin Pharmacol. 1992;42(2):121-5. [PubMed:1618240]
External Links
Human Metabolome Database
HMDB0015473
PubChem Compound
54682045
PubChem Substance
46505243
ChemSpider
10642393
PharmGKB
PA164749164

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ivax Pharmaceuticals
  • Pliva Inc.
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Choline mag trisal 1 gm tablet1.23USD tablet
Choline mag trisal 750 mg tablet0.81USD tablet
Choline mag trisal 500 mg tablet0.57USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP1.98ChemAxon
pKa (Strongest Acidic)2.79ChemAxon
pKa (Strongest Basic)-6.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.36 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity46.13 m3·mol-1ChemAxon
Polarizability12.38 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9852
Blood Brain Barrier-0.8993
Caco-2 permeable+0.5436
P-glycoprotein substrateSubstrate0.7681
P-glycoprotein inhibitor INon-inhibitor0.9522
P-glycoprotein inhibitor IINon-inhibitor0.6479
Renal organic cation transporterNon-inhibitor0.7147
CYP450 2C9 substrateNon-substrate0.7398
CYP450 2D6 substrateNon-substrate0.7764
CYP450 3A4 substrateSubstrate0.588
CYP450 1A2 substrateNon-inhibitor0.7658
CYP450 2C9 inhibitorNon-inhibitor0.8703
CYP450 2D6 inhibitorNon-inhibitor0.7642
CYP450 2C19 inhibitorNon-inhibitor0.8941
CYP450 3A4 inhibitorNon-inhibitor0.9072
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9752
Ames testNon AMES toxic0.7389
CarcinogenicityNon-carcinogens0.729
BiodegradationReady biodegradable0.5807
Rat acute toxicity2.3576 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8568
hERG inhibition (predictor II)Non-inhibitor0.7428
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as salicylic acids. These are ortho-hydroxylated benzoic acids.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Salicylic acids
Alternative Parents
Benzoic acids / Benzoyl derivatives / Phenoxides / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Cholines / Vinylogous acids / Tetraalkylammonium salts / 1,2-aminoalcohols / Carboxylic acid salts
show 7 more
Substituents
Salicylic acid / Benzoic acid / Benzoyl / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Choline / Phenol / Phenoxide / Tetraalkylammonium salt / Vinylogous acid
show 19 more
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Nizankowska E, Dworski R, Soja J, Szczeklik A: Salicylate pre-treatment attenuates intensity of bronchial and nasal symptoms precipitated by aspirin in aspirin-intolerant patients. Clin Exp Allergy. 1990 Nov;20(6):647-52. [PubMed:2083404]
  2. Simon RA: Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs. Curr Allergy Asthma Rep. 2004 Jan;4(1):17-24. [PubMed:14680616]
  3. Schwartz KA: Aspirin resistance: a review of diagnostic methodology, mechanisms, and clinical utility. Adv Clin Chem. 2006;42:81-110. [PubMed:17131625]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Simon RA: Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs. Curr Allergy Asthma Rep. 2004 Jan;4(1):17-24. [PubMed:14680616]
  2. Brzozowski T, Konturek PC, Sliwowski Z, Kwiecien S, Drozdowicz D, Pawlik M, Mach K, Konturek SJ, Pawlik WW: Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals. J Physiol Pharmacol. 2006 Sep;57 Suppl 3:67-79. [PubMed:17033106]
  3. Wang HJ, Liu XJ, Yang KX, Luo FM, Lou JY, Peng ZL: [Effects of nonsteroidal anti-inflammatory drug celecoxib on expression of cyclooxygenase-2 (COX-2) in ovarian carcinoma cell]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2006 Sep;37(5):757-60. [PubMed:17037745]
  4. Shen J, Gammon MD, Terry MB, Teitelbaum SL, Neugut AI, Santella RM: Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk. Breast Cancer Res. 2006;8(6):R71. [PubMed:17181859]
  5. Nakano M, Denda N, Matsumoto M, Kawamura M, Kawakubo Y, Hatanaka K, Hiramoto Y, Sato Y, Noshiro M, Harada Y: Interaction between cyclooxygenase (COX)-1- and COX-2-products modulates COX-2 expression in the late phase of acute inflammation. Eur J Pharmacol. 2007 Mar 22;559(2-3):210-8. Epub 2006 Dec 16. [PubMed:17258197]

Drug created on July 08, 2007 11:07 / Updated on October 01, 2018 13:03