Amlexanox
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| Clinical data | |
|---|---|
| Trade names | Aphthasol |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601017 |
| Routes of administration | Topical |
| ATC code | |
| Pharmacokineticdata | |
| Eliminationhalf-life | 3.5 hours |
| Excretion | Renal(17%) |
| Identifiers | |
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| CAS Number | |
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| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEBI | |
| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.230.878 |
| Chemical and physical data | |
| Formula | C16H14N2O4 |
| Molar mass | 298.298g·mol−1 |
| 3D model (JSmol) | |
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Amlexanox(trade nameAphthasol) is ananti-inflammatoryantiallergicimmunomodulatorused to treat recurrentaphthous ulcers(canker sores), and (in Japan) severalinflammatory 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 recurrentaphthous ulcersof 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 withBehçet disease.[7]
In Japan, it is used to treatbronchial asthma,allergicrhinitisandconjunctivitis.[8]
Contraindications
[edit]The drug is contraindicated in those with known allergies to it.[3]
Adverse effects
[edit]Amlexanox may cause a slightly painful stinging or burning sensation, nausea or diarrhea.[3]
Mechanism of action
[edit]Its mechanism of action is not well-determined, but it might inhibit inflammation by inhibiting the release ofhistamineandleukotrienes.[8]It has been shown to selectively inhibitTBK1andIKK-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 inglycated hemoglobinandfructosaminein obese patients withtype 2 diabetesandnonalcoholic fatty liver disease[10]
Chemistry
[edit]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 thegastrointestinal tract;an insignificant amount enters thebloodstreamthrough the ulcer itself. After a single 100 mg dose, mean maximumserumconcentration 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
[edit]Economics
[edit]A 2011 review found a one-week supply of amlexanox 5% paste to cost $30.[6]
Research
[edit]A review found that, as of July 2011[update],robust studies investigating its effectiveness alongside other canker sore treatments were still needed.[12]
Because it is aninhibitorof theprotein kinasesTBK1andIKK-ε,[9]which are implicated in theetiologyoftype II diabetesandobesity,[13]amlexanox may be a candidate for human clinical trials testing in relation to these diseases.[9]
Synthesis
[edit]
References
[edit]- ^"Amlexanox (Aphthasol®)".Archived fromthe originalon 20 November 2013.Retrieved20 November2013.
- ^Gonsalves WC, Chi AC, Neville BW (February 2007)."Common oral lesions: Part I. Superficial mucosal lesions".American Family Physician.75(4): 501–507.PMID17323710.
- ^abcde"Amlexanox".MedlinePlus.U.S. National Library of Medicine. February 2009.Retrieved12 February2013.
- ^abPlewa MC (March 2012)."Pediatric Aphthous Ulcers Treatment & Management".Medscape Reference.Medscape.Retrieved14 February2013.
- ^"Amlexanox".PubChem.U.S. National Library of Medicine.Retrieved12 February2013.
- ^abBailey 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.PMID21977491.
- ^Yousefi M, Ferringer T, Lee S, Bang D (July 2012)."Dermatologic Aspects of Behcet Disease Treatment & Management".Medscape Reference.Medscape.Retrieved14 February2013.
- ^abcdeBell J (2005). "Amlexanox for the treatment of recurrent aphthous ulcers".Clinical Drug Investigation.25(9): 555–566.doi:10.2165/00044011-200525090-00001.PMID17532700.S2CID24492356.
- ^abcReilly 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.PMC3594079.PMID23396211.
- ^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.PMC5663294.PMID28683283.
- ^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.
- ^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.PMID22258979.
- ^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.PMC2756060.PMID19737522.
- ^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.PMID3989816.