Cromoglicic acid (INN) (also referred to as cromolyn (USAN), cromoglycate (former BAN), or cromoglicate) is traditionally described as a mast cell stabilizer, and is commonly marketed as the sodium salt sodium cromoglicate or cromolyn sodium. This drug prevents the release of inflammatory chemicals such as histamine from mast cells.
Cromoglicic acid has been the non-corticosteroid treatment of choice in the treatment of asthma, for which it has largely been replaced by leukotriene receptor antagonists because of their convenience (and perceived safety). Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.[1]
Contents
1History
2Preparations
3Mechanism of action
4Synthesis
5References
History
Cromolyn sodium was discovered in 1965 by Roger Altounyan who was himself a lifelong asthma sufferer. It is considered a breakthrough drug in management of asthma, as the patients can be freed from steroids in many cases; however, it is mainly effective as a prophylaxis for allergic and exercise-induced asthma, not as a treatment for acute attacks. Altounyan was investigating certain plants and herbs which have bronchodilating properties. One such plant was khella (Ammi visnaga) which had been used as a muscle relaxant since ancient times in Egypt. Altounyan deliberately inhaled derivatives of the active ingredient khellin to determine if they could block his asthma attacks. After several years of trial he isolated an effective and safe asthma-preventing compound called cromolyn sodium.
Preparations
Cromoglicic acid is available in multiple forms:
as a nasal spray (Rynacrom(UK), Lomusol(France), Nasalcrom(US), Prevalin (non-direct version, NL) ) to treat allergic rhinitis.
in a nebulizer solution for aerosol administration to treat asthma.
as an inhaler (Intal) for preventive management of asthma.[2] The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant.[3] As stocks are depleted, this inhaler preparation will no longer be available to patients.[4] In the EU it is manufactured without CFCs by Sanofi, although it must be imported from Canada for USA residents.
as eye drops (Opticrom and Optrex Allergy (UK), Crolom, Cromolyn (Canada)) for allergic conjunctivitis[5]
in an oral form (Gastrocrom, Nalcrom) to treat mastocytosis,[6] mast cell activation syndrome, dermatographic urticaria and ulcerative colitis. Another oral product, Intercron (sodium cromoglicate in distilled water, from Zambon France), is used for food allergies.
Mechanism of action
"Cromolyn works because it prevents the release of mediators that would normally attract inflammatory cells and because it stabilizes the inflammatory cells. MCT mast cells found in the mucosa are stabilised."[7] Nedocromil is another mast cell stabilizer that also works in controlling asthma.
The underlying mechanism of action is not fully understood; for while cromoglicate stabilizes mast cells, this mechanism is probably not why it works in asthma.[8] Pharmaceutical companies have produced 20 related compounds that are equally or more potent at stabilising mast cells and none of them have shown any anti-asthmatic effect.[8] It is more likely that these work by inhibiting the response of sensory C fibers to the irritant capsaicin, inhibiting local axon reflexes involved in asthma, and may inhibit the release of preformed T cell cytokines and mediators involved in asthma. (see review by Garland, 1991)
It is known to somewhat inhibit chloride channels (37% ± 7%)[9] and thus may inhibit the:
exaggerated neuronal reflexes triggered by stimulation of irritant receptors on sensory nerve endings (e.g. exercise-induced asthma)
release of preformed cytokines from several type of inflammatory cells (T cells, eosinophils) in allergen-induced asthma
Note: Another chemical (NPPB: 5-nitro-2(3-phenyl) propylamino-benzoic acid) was shown, in the same study, to be a more effective chloride channel blocker.
Finally it may act by inhibiting calcium influx.
Cromoglicate is classified as a chromone.
Cromolyn is also being tested as a drug to treat insulin-induced lipoatrophy.[10][11] Cromolyn is also known to bind S100P protein and disrupt the interaction with RAGE.[12][13]
Synthesis
References
^Fanta CH (March 2009). "Asthma". New England Journal of Medicine. 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689. Review.
^Schwartz HJ, Blumenthal M, Brady R, et al. (April 1996). "A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment?". Chest. 109 (4): 945–52. doi:10.1378/chest.109.4.945. PMID 8635375.
^Eric Carter (July 31, 2009). "King Pharmaceuticals: Dear Healthcare Professionals" (PDF). Food and Drug Administration. King Pharmaceuticals. Retrieved May 28, 2012.
^Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A (2015). "Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis". Cochrane Database Syst Rev. 6: CD009566. doi:10.1002/14651858.CD009566.pub2. PMID 26028608.CS1 maint: Uses authors parameter (link)
^Horan RF, Sheffer AL, Austen KF (May 1990). "Cromolyn sodium in the management of systemic mastocytosis". J. Allergy Clin. Immunol. 85 (5): 852–5. doi:10.1016/0091-6749(90)90067-E. PMID 2110198.
^Werner's Pathophysiology page 224
^ abH. P. Rang et al., Pharmacology, Fifth Edition. (2003) ISBN 0-443-07145-4
^Heinke, S; Szucs G; Norris A; Droogmans G; Nilius B (August 1995). "Inhibition of volume-activated chloride currents in endothelial cells by chromones". Br J Pharmacol. 115 (8): 1393–8. doi:10.1111/j.1476-5381.1995.tb16629.x. PMC 1908889. PMID 8564197.
^Phua, EJ; Lopez, X; Ramus, J; Goldfine, AB (December 2013). "Cromolyn sodium for insulin-induced lipoatrophy: old drug, new use" (PDF). Diabetes Care. 36 (12): e204–5. doi:10.2337/dc13-1123. PMC 3836099. PMID 24265375.
^Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin (2014-08-01). "Structural Insights into Calcium-Bound S100P and the V Domain of the RAGE Complex". PLOS ONE. 9 (8): e103947. doi:10.1371/journal.pone.0103947. ISSN 1932-6203. PMC 4118983. PMID 25084534.
^Penumutchu, Srinivasa R.; Chou, Ruey-Hwang; Yu, Chin (2014-10-17). "Interaction between S100P and the anti-allergy drug cromolyn". Biochemical and Biophysical Research Communications. 454 (3): 404–409. doi:10.1016/j.bbrc.2014.10.048. ISSN 1090-2104. PMID 25450399.
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Antidiarrheals, intestinal anti-inflammatory and anti-infective agents (A07)
5. 12歳未満の小児における慢性喘息：コントローラ剤 chronic asthma in children younger than 12 years controller medications
English Journal
Cromolyn as surface active drug (surfadrug): Effect of the self-association on diffusion and percutaneous permeation.
Tavano L1, Nicoletta FP2, Picci N2, Muzzalupo R3.
Colloids and surfaces. B, Biointerfaces.Colloids Surf B Biointerfaces.2016 Mar 1;139:132-7. doi: 10.1016/j.colsurfb.2015.12.010. Epub 2015 Dec 8.
Cromolyn sodium, or disodium cromoglycate (CS), is a surface active drug: a pharmacologically active compound with an amphiphilic nature. At certain conditions it is able to self-associate in several kind of supramolecular aggregates. Since CS could play the role of both carrier and drug, bypassing
Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory activity in Nostochopsis lobatus MAC0804NAN.
Yamaguchi Y1, Koketsu M2.
Journal of bioscience and bioengineering.J Biosci Bioeng.2016 Mar;121(3):345-8. doi: 10.1016/j.jbiosc.2015.07.008. Epub 2015 Aug 18.
An active substance with high hyaluronidase inhibitory effect was isolated from the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and characterized. The active component in the hot water extract was purified by anion exchange and gel filtration chromatography and was found to be a pol
Journal of microencapsulation.J Microencapsul.2016 Feb 17:1-12. [Epub ahead of print]
Cromolyn sodium (CS), a mast cell stabiliser, is widely employed for the prevention and treatment of allergic conditions. However, high hydrophilicity and poor oral permeability hinder its oral clinical translation. Here, solid lipid nanoparticles (SLNs) have been developed for the purpose of oral b
Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory activity in Nostochopsis lobatus MAC0804NAN
Yamaguchi Yuji,Koketsu Mamoru
Journal of bioscience and bioengineering 121(3), 345-348, 2016-03
… against hyaluronidase of the purified polysaccharide was 7.18 μg/ml whose inhibitory activity is 14.5 times stronger than that of disodiumcromoglycate (DSCG), an anti-allergy medication. …
Cox JS. Disodium cromoglycate (FPL 670) ('Intal'): a specific inhibitor of reaginic antibody-antigen mechanisms. Nature. 1967 Dec 30; 216 (5122):1328–1329. [PubMed] Chen JL, Moore N, Norman PS, Van Metre TE., Jr Disodium ...
