Chemistry:Amlexanox
| Clinical data | |
|---|---|
| Trade names | Aphthasol |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601017 |
| Routes of administration | Topical |
| ATC code | |
| Pharmacokinetic data | |
| Elimination half-life | 3.5 hours |
| Excretion | Renal (17%) |
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| CAS Number | |
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| IUPHAR/BPS | |
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| Chemical and physical data | |
| Formula | C16H14N2O4 |
| Molar mass | 298.298 g·mol−1 |
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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
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
The drug is contraindicated in those with known allergies to it.[3]
Adverse effects
Amlexanox may cause a slightly painful stinging or burning sensation, nausea or diarrhea.[3]
Mechanism of action
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
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
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
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
Economics
A 2011 review found a one-week supply of amlexanox 5% paste to cost $30.[6]
Research
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
References
- ↑ "Amlexanox (Aphthasol®)". http://www.childrensdmc.org/HealthLibrary/default.aspx?sid=1&pTitle=&ContentTypeID=26&ContentID=665&pTitle=Drug&alpha=A&AdditionalTitle=Aphthasol%C2%AE.
- ↑ "Common oral lesions: Part I. Superficial mucosal lesions". American Family Physician 75 (4): 501–507. February 2007. PMID 17323710. http://www.aafp.org/afp/2007/0215/p501.html.
- ↑ 3.0 3.1 3.2 3.3 3.4 "Amlexanox". MedlinePlus. U.S. National Library of Medicine. February 2009. https://www.nlm.nih.gov/medlineplus/druginfo/meds/a601017.html.
- ↑ 4.0 4.1 Plewa MC (March 2012). "Pediatric Aphthous Ulcers Treatment & Management". Medscape Reference. Medscape. http://emedicine.medscape.com/article/909213-treatment.
- ↑ "Amlexanox". PubChem. U.S. National Library of Medicine. https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?q=all&cid=2161#ec.
- ↑ 6.0 6.1 "Clinical inquiry. What is the most effective way to treat recurrent canker sores?". The Journal of Family Practice 60 (10): 621–632. October 2011. PMID 21977491. http://www.jfponline.com/Pages.asp?AID=9930.
- ↑ "Dermatologic Aspects of Behcet Disease Treatment & Management". Medscape Reference. Medscape. July 2012. http://emedicine.medscape.com/article/1122381-treatment.
- ↑ 8.0 8.1 8.2 8.3 8.4 "Amlexanox for the treatment of recurrent aphthous ulcers". Clinical Drug Investigation 25 (9): 555–566. 2005. doi:10.2165/00044011-200525090-00001. PMID 17532700.
- ↑ 9.0 9.1 9.2 "An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice". Nature Medicine 19 (3): 313–321. March 2013. doi:10.1038/nm.3082. PMID 23396211.
- ↑ "Inhibition of IKKɛ and TBK1 Improves Glucose Control in a Subset of Patients with Type 2 Diabetes". Cell Metabolism 26 (1): 157–170.e7. July 2017. doi:10.1016/j.cmet.2017.06.006. PMID 28683283.
- ↑ Vora KR, Khandwala A, Smith CG, "Methods of treating aphthous ulcers and other mucocutaneous disorders with amlexanox", US patent 5362737, published 1994-11-08, assigned to Chemex Pharmaceuticals, Inc.
- ↑ "Topical treatments for HIV-related oral ulcers". The Cochrane Database of Systematic Reviews 1: CD007975. January 2012. doi:10.1002/14651858.CD007975.pub2. PMID 22258979.
- ↑ "The protein kinase IKKepsilon regulates energy balance in obese mice". Cell 138 (5): 961–975. September 2009. doi:10.1016/j.cell.2009.06.046. PMID 19737522.
- ↑ "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. May 1985. doi:10.1021/jm50001a005. PMID 3989816.