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Amlexanox

From Wikipedia, the free encyclopedia
Amlexanox
Clinical data
Trade namesAphthasol
AHFS/Drugs.comMonograph
MedlinePlusa601017
Routes of
administration
Topical
ATC code
Pharmacokinetic data
Elimination half-life3.5 hours
ExcretionRenal (17%)
Identifiers
  • 2-amino-7-isopropyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.230.878 Edit this at Wikidata
Chemical and physical data
FormulaC16H14N2O4
Molar mass298.298 g·mol−1
3D model (JSmol)
  • O=C1c3cc(ccc3Oc2nc(c(cc12)C(=O)O)N)C(C)C
  • InChI=1S/C16H14N2O4/c1-7(2)8-3-4-12-9(5-8)13(19)10-6-11(16(20)21)14(17)18-15(10)22-12/h3-7H,1-2H3,(H2,17,18)(H,20,21) checkY
  • Key:SGRYPYWGNKJSDL-UHFFFAOYSA-N checkY
  (verify)

Amlexanox (trade name Aphthasol) is an anti-inflammatory antiallergic immunomodulator used to treat recurrent aphthous ulcers (canker sores), and (in Japan) several inflammatory conditions. This drug has been discontinued in the U.S.[1]

Medical uses

[edit]

Amlexanox is the active ingredient in a common topical treatment for recurrent aphthous ulcers of the mouth (canker sores),[2] reducing both healing time[3] and pain.[4] Amlexanox 5% paste is well tolerated,[5] and is typically applied four times per day directly on the ulcers.[3] A 2011 review found it to be the most effective treatment of the eight treatments investigated for recurrent canker sores.[6] It is also used to treat ulcers associated with Behçet disease.[7]

In Japan, it is used to treat bronchial asthma, allergic rhinitis and conjunctivitis.[8]

Contraindications

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The drug is contraindicated in those with known allergies to it.[3]

Adverse effects

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Amlexanox may cause a slightly painful stinging or burning sensation, nausea or diarrhea.[3]

Mechanism of action

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Its mechanism of action is not well-determined, but it might inhibit inflammation by inhibiting the release of histamine and leukotrienes.[8] It has been shown to selectively inhibit TBK1 and IKK-ε, producing reversible weight loss and improved insulin sensitivity, reduced inflammation and attenuated hepatic steatosis without affecting food intake in obese mice.[9] It produced a statistically significant reduction in glycated hemoglobin and fructosamine in obese patients with type 2 diabetes and nonalcoholic fatty liver disease[10]

Chemistry

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The chemical itself is an odorless, white to yellowish-white powder.[8]

The 5% preparation for patient use is an adherent beige paste,[3][8] and it is also available in some countries as a tablet that adheres to the ulcer in the mouth.[4]

Pharmacokinetics

[edit]

Amlexanox applied to an aphthous ulcer is largely absorbed through the gastrointestinal tract; an insignificant amount enters the bloodstream through the ulcer itself. After a single 100 mg dose, mean maximum serum concentration occurs 2.4 +/- 0.9 hours after application, with a half-life of elimination (through urine) of 3.5 +/- 1.1 hours. With multiple daily applications (four doses per day), steady state serum levels occur after one week, with no accumulation occurring after four weeks.[8]

History

[edit]

The patent for its use as a treatment for aphthous ulcers was issued in November 1994 to inventors Kakubhai R. Vora, Atul Khandwala and Charles G. Smith, and assigned to Chemex Pharmaceuticals, Inc.[11]

Society and culture

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Economics

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A 2011 review found a one-week supply of amlexanox 5% paste to cost $30.[6]

Research

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A review found that, as of July 2011, robust studies investigating its effectiveness alongside other canker sore treatments were still needed.[12]

Because it is an inhibitor of the protein kinases TBK1 and IKK-ε,[9] which are implicated in the etiology of type II diabetes and obesity,[13] amlexanox may be a candidate for human clinical trials testing in relation to these diseases.[9]

Synthesis

[edit]
Amlexanox synthesis:[14]

References

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  1. ^ "Amlexanox (Aphthasol®)". Archived from the original on 20 November 2013. Retrieved 20 November 2013.
  2. ^ Gonsalves WC, Chi AC, Neville BW (February 2007). "Common oral lesions: Part I. Superficial mucosal lesions". American Family Physician. 75 (4): 501–507. PMID 17323710.
  3. ^ a b c d e "Amlexanox". MedlinePlus. U.S. National Library of Medicine. February 2009. Retrieved 12 February 2013.
  4. ^ a b Plewa MC (March 2012). "Pediatric Aphthous Ulcers Treatment & Management". Medscape Reference. Medscape. Retrieved 14 February 2013.
  5. ^ "Amlexanox". PubChem. U.S. National Library of Medicine. Retrieved 12 February 2013.
  6. ^ a b Bailey J, McCarthy C, Smith RF (October 2011). "Clinical inquiry. What is the most effective way to treat recurrent canker sores?". The Journal of Family Practice. 60 (10): 621–632. PMID 21977491.
  7. ^ Yousefi M, Ferringer T, Lee S, Bang D (July 2012). "Dermatologic Aspects of Behcet Disease Treatment & Management". Medscape Reference. Medscape. Retrieved 14 February 2013.
  8. ^ a b c d e Bell J (2005). "Amlexanox for the treatment of recurrent aphthous ulcers". Clinical Drug Investigation. 25 (9): 555–566. doi:10.2165/00044011-200525090-00001. PMID 17532700. S2CID 24492356.
  9. ^ a b c Reilly SM, Chiang SH, Decker SJ, Chang L, Uhm M, Larsen MJ, et al. (March 2013). "An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice". Nature Medicine. 19 (3): 313–321. doi:10.1038/nm.3082. PMC 3594079. PMID 23396211.
  10. ^ Oral EA, Reilly SM, Gomez AV, Meral R, Butz L, Ajluni N, et al. (July 2017). "Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes". Cell Metabolism. 26 (1): 157–170.e7. doi:10.1016/j.cmet.2017.06.006. PMC 5663294. PMID 28683283.
  11. ^ US patent 5362737, Vora KR, Khandwala A, Smith CG, "Methods of treating aphthous ulcers and other mucocutaneous disorders with amlexanox", published 1994-11-08, assigned to Chemex Pharmaceuticals, Inc. 
  12. ^ Kuteyi T, Okwundu CI (January 2012). Kuteyi T (ed.). "Topical treatments for HIV-related oral ulcers". The Cochrane Database of Systematic Reviews. 1: CD007975. doi:10.1002/14651858.CD007975.pub2. PMID 22258979.
  13. ^ Chiang SH, Bazuine M, Lumeng CN, Geletka LM, Mowers J, White NM, et al. (September 2009). "The protein kinase IKKepsilon regulates energy balance in obese mice". Cell. 138 (5): 961–975. doi:10.1016/j.cell.2009.06.046. PMC 2756060. PMID 19737522.
  14. ^ Nohara A, Ishiguro T, Ukawa K, Sugihara H, Maki Y, Sanno Y (May 1985). "Studies on antianaphylactic agents. 7. Synthesis of antiallergic 5-oxo-5H-[1]benzopyrano[2,3-b]pyridines". Journal of Medicinal Chemistry. 28 (5): 559–568. doi:10.1021/jm50001a005. PMID 3989816.