Cromoglicic acid

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Cromoglicic acid
Trade namesCrolom, Nasalcrom, others
Other namesCromolyn, cromolyn sodium, cromoglycate, cromoglicate
  • 5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
Clinical data
Drug classMast cell stabilizer[1]
Main usesAsthma, allergic rhinitis, allergic conjunctivitis, and systemic mastocytosis[1][2]
Side effectsInhaled: Stuffy nose, cough, nausea[1]
Eye&nose: Burning, irritation[2]
  • AU: B1
  • US: B (No risk in non-human studies)
Routes of
Nasal spray, inhaled, eye drop
External links
AHFS/Drugs.comInahled: Monograph
Eye&nose: Monograph
License data
Legal status
  • AU: S2 (Pharmacy medicine)
  • UK: Inhaler POM; eye OTC
  • US: OTC Nasal; eye, inhaler: Rx only
Elimination half-life1.3 hours
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

Cromoglicic acid, also known as cromolyn, is a medication used to treat asthma, allergic rhinitis, allergic conjunctivitis, and systemic mastocytosis.[1][2] In asthma it is not a preferred treatment.[1] It is inhaled, or used as a nasal spray or eye drop[1][2]

Common side effects when inhaled include stuffy nose, cough, and nausea.[1] Common side effects when placed in the nose or eyes include burning or irritation.[2] Other side effects may include anaphylaxis.[1] While there is no evidence of harm in pregnancy, such use has not been well studied.[3] It is a mast cell stabilizer, which decreases the release of histamine.[1][4]

Cromoglicic acid was made in 1965 and came into medical use in the United States in 1973.[4] It is available as a generic medication.[5] In the United States 120 containers of 5 ml to inhale costs about 130 USD; while 10 ml of eye drops costs about 9 USD as of 2022.[6][5]

Medical uses


In asthma it has been used long-term to prevent worseing in mild-to-moderate disease. Decrease in the frequency and severity of attacks is more likely in extrinsic (atopic) and exercise-induced asthma, especially in younger patients. Therapeutic benefit (when it occurs) develops slowly over 2–4 weeks and lasts 1–2 weeks after discontinuing. However, it is less effective than inhaled steroids and is seldom used now.

It is given four times daily, but does not provide additive benefit in combination with inhaled corticosteroids.[7]


Allergic rhinitis: Cromoglycate is not a nasal decongestant, but regular 4 times daily use as a nasal spray produces some symptomatic improvement in many patients after 4–6 weeks. The need for nasal decongestants may be reduced.

Allergic conjunctivitis: Regular use as eye drops is beneficial in some chronic cases.

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."[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. (see review by Garland, 1991)

It is known to somewhat inhibit chloride channels (37% ± 7%)[10] 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.[11][12] Cromolyn is also known to bind S100P protein and disrupt the interaction with RAGE.[13][14]


Cromolyn sodium was discovered in 1965 by Roger Altounyan who himself 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.

Society and culture


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, Fisons Pharmaceuticals, UK) for preventive management of asthma.[15] The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant.[16] As stocks are depleted, this inhaler preparation will no longer be available to patients.[17] 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[18]
  • in an oral form (Gastrocrom, Nalcrom) to treat mastocytosis,[19] 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.


Cromoglicic acid synthesis.


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Cromolyn (Systemic, Oral Inhalation) Monograph for Professionals". Archived from the original on 18 January 2021. Retrieved 7 January 2022.
  2. 2.0 2.1 2.2 2.3 2.4 "Cromolyn (EENT) Monograph for Professionals". Archived from the original on 26 January 2021. Retrieved 7 January 2022.
  3. "Cromolyn Use During Pregnancy". Archived from the original on 25 November 2020. Retrieved 7 January 2022.
  4. 4.0 4.1 Ebadi, Manuchair (31 October 2007). Desk Reference of Clinical Pharmacology. CRC Press. p. 485. ISBN 978-1-4200-4744-8. Archived from the original on 11 January 2022. Retrieved 7 January 2022.
  5. 5.0 5.1 "Cromolyn Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 7 January 2022.
  6. "Cromolyn Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 7 January 2022.
  7. Fanta CH (March 2009). "Asthma". New England Journal of Medicine. 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689. Review.
  8. Werner's Pathophysiology page 224
  9. 9.0 9.1 H. P. Rang et al., Pharmacology, Fifth Edition. (2003) ISBN 0-443-07145-4
  10. 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.
  11. 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. Archived (PDF) from the original on 2018-11-04. Retrieved 2021-05-05.
  12. "Archive copy". Archived from the original on 2013-12-24. Retrieved 2021-05-05.{{cite web}}: CS1 maint: archived copy as title (link)
  13. 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. Bibcode:2014PLoSO...9j3947P. doi:10.1371/journal.pone.0103947. ISSN 1932-6203. PMC 4118983. PMID 25084534.
  14. 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.
  15. 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. Archived from the original on 2013-04-14.
  16. Eric Carter (July 31, 2009). "King Pharmaceuticals: Dear Healthcare Professionals" (PDF). Food and Drug Administration. King Pharmaceuticals. Archived (PDF) from the original on September 20, 2012. Retrieved May 28, 2012.
  17. "Intal Inhaler discontinued - MPR". Archived from the original on 2012-04-22. Retrieved 2012-05-28.
  18. 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" (PDF). Cochrane Database Syst Rev. 6 (6): CD009566. doi:10.1002/14651858.CD009566.pub2. hdl:2164/6048. PMID 26028608. Archived from the original on 2021-08-28. Retrieved 2021-05-05.{{cite journal}}: CS1 maint: uses authors parameter (link)
  19. 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.

External links