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Cromoglicic acid

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Cromoglicic acid
Clinical data
AHFS/Drugs.comInternational Drug Names
License data
  • AU: B1
Routes of
topical: oral, nasal spray, inhaled, eye drops
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy medicine)
  • UK: inhaler POM; eye OTC
  • US: OTC nasal; eye, inhaler: Rx only
Pharmacokinetic data
Elimination half-life1.3 hours
  • 5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard100.036.602 Edit this at Wikidata
Chemical and physical data
Molar mass468.370 g·mol−1
3D model (JSmol)
  • O=C(O)C=4Oc3cccc(OCC(O)COc2cccc1O/C(=C\C(=O)c12)C(=O)O)c3C(=O)C=4
  • InChI=1S/C23H16O11/c24-11(9-31-14-3-1-5-16-20(14)12(25)7-18(33-16)22(27)28)10-32-15-4-2-6-17-21(15)13(26)8-19(34-17)23(29)30/h1-8,11,24H,9-10H2,(H,27,28)(H,29,30) checkY
 ☒NcheckY (what is this?)  (verify)

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.

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 asthma attacks.[citation needed]

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acid has been the non-corticosteroid treatment of choice in the treatment of asthma, for which it has largely been replaced by leukotriene receptor antagonists because of their safety and convenience. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.[1]


Cromolyn was discovered in 1965 by Roger Altounyan, a pharmacologist who had asthma. 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.[2]


Cromoglicic acid is available in multiple forms:

  • as a nasal spray (Rynacrom (UK), Lomusol (France), Nasalcrom (the only over-the-counter form, US), Prevalin (non-direct version, NL)) to treat allergic rhinitis.
  • in a nebulizer solution for aerosol administration to treat asthma.
  • as an inhaler (Intal, Fisons Pharmaceuticals, UK) for preventive management of asthma.[3] The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant.[4] As stocks are depleted, this inhaler preparation will no longer be available to patients.[5] In the EU it is manufactured without CFCs by Sanofi, although it must be imported from Canada or Mexico for USA residents.
  • as eye drops (Opticrom and Optrex Allergy (UK), Crolom, Cromolyn (Canada)) for allergic conjunctivitis[6]
  • in an oral form (Gastrocrom, Nalcrom) to treat mastocytosis,[7] 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[edit]

"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."[8] 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.[9] 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.[9] 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.[10]

It is known to somewhat inhibit chloride channels (37% ± 7%)[11] 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[12][13] and Alzheimer's disease in combination with Ibuprofen.[14] Cromolyn is also known to bind S100P protein and disrupt the interaction with RAGE.[15][16]


Cromoglicic acid synthesis.

See also[edit]

Visnaga daucoides


  1. ^ Fanta CH (March 2009). "Asthma". The New England Journal of Medicine. 360 (10): 1002–1014. doi:10.1056/NEJMra0804579. PMID 19264689. Review.
  2. ^ . doi:10.1016/S0954-6111(89)80245-8. {{cite journal}}: Cite journal requires |journal= (help); Missing or empty |title= (help)
  3. ^ Schwartz HJ, Blumenthal M, Brady R, Braun S, Lockey R, Myers D, 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): 945–952. doi:10.1378/chest.109.4.945. PMID 8635375. Archived from the original on 2013-04-14.
  4. ^ Carter E (July 31, 2009). "King Pharmaceuticals: Dear Healthcare Professionals" (PDF). Food and Drug Administration. King Pharmaceuticals. Retrieved May 28, 2012.
  5. ^ "Intal Inhaler discontinued - MPR". Empr.com. 4 August 2009. Retrieved 2012-05-28.
  6. ^ Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A (June 2015). "Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis". The Cochrane Database of Systematic Reviews. 2015 (6): CD009566. doi:10.1002/14651858.CD009566.pub2. hdl:2164/6048. PMC 10616535. PMID 26028608.
  7. ^ Horan RF, Sheffer AL, Austen KF (May 1990). "Cromolyn sodium in the management of systemic mastocytosis". The Journal of Allergy and Clinical Immunology. 85 (5): 852–855. doi:10.1016/0091-6749(90)90067-E. PMID 2110198.
  8. ^ Werner's Pathophysiology page 224
  9. ^ a b Rang RP, Dale MM, Ritter JM, Keith P (2003). Pharmacology (Fifth ed.). Churchill Livingstone. ISBN 978-0-443-07145-4.
  10. ^ Garland LG (1991). "Pharmacology of Prophylactic Anti-Asthma Drugs". Pharmacology of Asthma. Handbook of Experimental Pharmacology. Vol. 98. pp. 261–290. doi:10.1007/978-3-642-75855-3_9. ISBN 978-3-642-75857-7.
  11. ^ Heinke S, Szücs G, Norris A, Droogmans G, Nilius B (August 1995). "Inhibition of volume-activated chloride currents in endothelial cells by chromones". British Journal of Pharmacology. 115 (8): 1393–1398. doi:10.1111/j.1476-5381.1995.tb16629.x. PMC 1908889. PMID 8564197.
  12. ^ Phua EJ, Lopez X, Ramus J, Goldfine AB (December 2013). "Cromolyn sodium for insulin-induced lipoatrophy: old drug, new use". Diabetes Care. 36 (12): e204–e205. doi:10.2337/dc13-1123. PMC 3836099. PMID 24265375.
  13. ^ Yasgur BS (18 December 2013). "A Surprising Option for Managing Insulin-Induced Lipoatrophy".
  14. ^ "Alzt-Op1". Alzforum.
  15. ^ Penumutchu SR, Chou RH, Yu C (2014-08-01). "Structural insights into calcium-bound S100P and the V domain of the RAGE complex". PLOS ONE. 9 (8): e103947. Bibcode:2014PLoSO...9j3947P. doi:10.1371/journal.pone.0103947. PMC 4118983. PMID 25084534.
  16. ^ Penumutchu SR, Chou RH, Yu C (November 2014). "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. PMID 25450399.

External links[edit]