Misplaced Pages

This is an old revision of this page, as edited by Beetstra (talk | contribs) at 09:18, 31 October 2011 (Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Cromoglicic acid

Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy category	B
Routes of administration	topical: oral, nasal spray, inhaled, eye drops
ATC code	A07EB01 (WHO) D11AH03 (WHO) R01AC01 (WHO) R03BC01 (WHO) S01GX01 (WHO)
Legal status
Legal status	inhaler POM, eye OTC(UK) nasal OTC, eye, inhaler Rx(US)
Pharmacokinetic data
Bioavailability	1%
Elimination half-life	1.3 hours
Identifiers
IUPAC name 5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4H-chromene-2-carboxylic acid)
CAS Number	16110-51-3
PubChem CID	2882
ChemSpider	2779
UNII	Y0TK0FS77W
KEGG	D07753
ChEBI	CHEBI:59773
CompTox Dashboard (EPA)	DTXSID4022860
ECHA InfoCard	100.036.602
Chemical and physical data
Formula	C23H16O11
Molar mass	468.367 g/mol g·mol
3D model (JSmol)	Interactive image
SMILES O=C(O)C=4Oc3cccc(OCC(O)COc2cccc1O/C(=C\C(=O)c12)C(=O)O)c3C(=O)C=4
InChI 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) Key:IMZMKUWMOSJXDT-UHFFFAOYSA-N
(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.

Because of their convenience (and perceived safety), leukotriene receptor antagonists have largely replaced it as the non-corticosteroid treatment of choice in the treatment of asthma. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.

History

Cromolyn sodium was discovered by Dr. 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. Dr. 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. Dr. 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), Nasalcrom, Prevalin (Netherlands)) to treat allergic rhinitis.

• in a nebulizer solution for aerosol administration to treat asthma.

• as an inhaler (Intal) for preventive management of asthma. The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant. As stocks are depleted, this inhaler preparation will no longer be available to patients. In the EU it is manufactured without CFCs by Sanofi-Aventis, although it must be imported from Canada for USA residents.

• as eye drops (Opticrom and Optrex Allergy (UK), Crolom) for allergic conjunctivitis

• in an oral form (Gastrocrom) to treat mastocytosis, 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." 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. 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. It is more likely that these work by inhibiting the response of sensory C fibres 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%) 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.

References

1. Fanta CH (2009). "Asthma". New England Journal of Medicine. 360 (10): 1002–14. doi:10.1056/NEJMra0804579. PMID 19264689. {{cite journal}}: Unknown parameter |month= ignored (help) Review.
2. Schwartz HJ, Blumenthal M, Brady R; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
3. http://www.empr.com/Intal-Inhaler-discontinued/article/141142/
4. Horan RF, Sheffer AL, Austen KF (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
5. Werner's Pathophysiology page 224
6. ^ H. P. Rang et al., Pharmacology, Fifth Edition. (2003) ISBN 0-443-07145-4
7. Heinke, S (1995). "Inhibition of volume-activated chloride currents in endothelial cells by chromones". Br J Pharmacol. 115 (8): 1393–8. PMC 1908889. PMID 8564197. {{cite journal}}: Cite has empty unknown parameter: |quotes= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

• Mast cell stabilizers
• Carboxylic acids
• Phenol ethers
• Chromones