Cromoglicic acid: Difference between revisions

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}

{{Infobox drug

| verifiedrevid = 458268085

| image2 = Cromolyn ball-and-stick animation.gif

| pregnancy_AU = B1

| pregnancy_category =

| legal_AU = S2

| legal_UK_comment = inhaler POM; eye OTC

| legal_US = OTC

| legal_US_comment = nasal; eye, inhaler: Rx only<!-- OTC / Rx-only -->

| licence_US = Cromolyn

| legal_status =

| excretion =

| IUPHAR_ligand = 7608

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB01003

| KEGG_Ref = {{keggcite|correct|kegg}}

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 74

<!--Chemical data-->

| C=23 | H=16 | O=11

'''Cromoglicic acid''' ([[International Nonproprietary Name|INN]])—also referred to as '''cromolyn''' ([[United States Adopted Name|USAN]]), '''cromoglycate''' (former [[British Approved Name|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 [[inflammation|inflammatory]] chemicals such as [[histamine]] from [[mast cell]]s.

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.{{cn|date=March 2024}}

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acid has been the non-[[corticosteroid]] treatment of choice in the treatment of [[asthma]], for which it has largely been replaced by [[leukotriene receptor antagonist]]s because of their safety and convenience. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.<ref>{{cite journal | vauthors = Fanta CH | title = Asthma | journal = The New England Journal of Medicine | volume = 360 | issue = 10 | pages = 1002–1014 | date = March 2009 | pmid = 19264689 | doi = 10.1056/NEJMra0804579 }} Review.</ref>

Cromolyn was discovered in 1965 by [[Roger Altounyan]], a [[Pharmacology|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.<ref name="v055">{{cite journal | last=Kuzemko | first=J.A. | title=Twenty years of sodium cromoglycate treatment: a short review | journal=Respiratory Medicine | volume=83 | date=1989 | doi=10.1016/S0954-6111(89)80245-8 | pages=11–16}}</ref>

* 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]].

* as an [[inhaler]] (Intal, Fisons Pharmaceuticals, UK) for preventive management of [[asthma]].<ref name="pmid8635375">{{cite journal | vauthors = Schwartz HJ, Blumenthal M, Brady R, Braun S, Lockey R, Myers D, Mansfield L, Mullarkey M, Owens G, Ratner P, Repsher L, van As A | display-authors = 6 | title = A comparative study of the clinical efficacy of nedocromil sodium and placebo. How does cromolyn sodium compare as an active control treatment? | journal = Chest | volume = 109 | issue = 4 | pages = 945–952 | date = April 1996 | pmid = 8635375 | doi = 10.1378/chest.109.4.945 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=8635375 | url-status = dead | archive-url = https://archive.today/20130414105126/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=8635375 | archive-date = 2013-04-14 }}</ref> The maker of Intal, King Pharmaceuticals, has discontinued manufacturing the inhaled form, cromolyn sodium inhalation aerosol, due to issues involving CFC-free propellant.<ref>{{cite web |url=https://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/UCM175032.pdf |title=King Pharmaceuticals: Dear Healthcare Professionals | vauthors = Carter E |date=July 31, 2009 |work=Food and Drug Administration |publisher=King Pharmaceuticals |access-date=May 28, 2012}}</ref> As stocks are depleted, this inhaler preparation will no longer be available to patients.<ref>{{cite web|url=http://www.empr.com/Intal-Inhaler-discontinued/article/141142/ |title=Intal Inhaler discontinued - MPR |date=4 August 2009 |publisher=Empr.com |access-date=2012-05-28}}</ref> In the EU it is manufactured without CFCs by [[Sanofi]], although it must be imported from Canada or Mexico for USA residents.

* as [[eye drop]]s (Opticrom and Optrex Allergy (UK), Crolom, Cromolyn (Canada)) for [[allergic conjunctivitis]]<ref name="Castillo">{{cite journal | vauthors = Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A | title = Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 6 | pages = CD009566 | date = June 2015 | pmid = 26028608 | doi = 10.1002/14651858.CD009566.pub2 | pmc = 10616535 | hdl-access = free | hdl = 2164/6048 }}</ref>

* in an oral form (Gastrocrom, Nalcrom) to treat [[mastocytosis]],<ref name="pmid2110198">{{cite journal | vauthors = Horan RF, Sheffer AL, Austen KF | title = Cromolyn sodium in the management of systemic mastocytosis | journal = The Journal of Allergy and Clinical Immunology | volume = 85 | issue = 5 | pages = 852–855 | date = May 1990 | pmid = 2110198 | doi = 10.1016/0091-6749(90)90067-E }}</ref> [[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.

"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."<ref>Werner's Pathophysiology page 224</ref> [[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.<ref name="rang">{{cite book | vauthors = Rang RP, Dale MM, Ritter JM, Keith P | title = Pharmacology | edition = Fifth | date = 2003 | publisher = Churchill Livingstone | isbn = 978-0-443-07145-4 }}</ref> 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.<ref name="rang"/> 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.<ref>{{cite book | vauthors = Garland LG | chapter = Pharmacology of Prophylactic Anti-Asthma Drugs | title = Pharmacology of Asthma | series = Handbook of Experimental Pharmacology | date = 1991 | volume = 98 | pages = 261–290 | doi = 10.1007/978-3-642-75855-3_9 | isbn = 978-3-642-75857-7 }}</ref>

It is known to somewhat inhibit [[chloride channels]] (37% ± 7%)<ref>{{cite journal | vauthors = Heinke S, Szücs G, Norris A, Droogmans G, Nilius B | title = Inhibition of volume-activated chloride currents in endothelial cells by chromones | journal = British Journal of Pharmacology | volume = 115 | issue = 8 | pages = 1393–1398 | date = August 1995 | pmid = 8564197 | pmc = 1908889 | doi = 10.1111/j.1476-5381.1995.tb16629.x }}</ref> and thus ''may'' inhibit the:

Cromolyn is also being tested as a drug to treat [[Lipodystrophy#Insulin injections|insulin-induced lipoatrophy]]<ref>{{cite journal | vauthors = Phua EJ, Lopez X, Ramus J, Goldfine AB | title = Cromolyn sodium for insulin-induced lipoatrophy: old drug, new use | journal = Diabetes Care | volume = 36 | issue = 12 | pages = e204–e205 | date = December 2013 | pmid = 24265375 | pmc = 3836099 | doi = 10.2337/dc13-1123 }}</ref><ref>{{Cite web | vauthors = Yasgur BS |url=http://www.empr.com/a-surprising-option-for-managing-insulin-induced-lipoatrophy/article/325863/|title=A Surprising Option for Managing Insulin-Induced Lipoatrophy|date=18 December 2013}}</ref> and [[Alzheimer's disease]] in combination with [[Ibuprofen]].<ref>{{cite web | url=https://www.alzforum.org/therapeutics/alzt-op1 | title=Alzt-Op1 | work = Alzforum }}</ref> Cromolyn is also known to bind S100P protein and disrupt the interaction with [[RAGE (receptor)|RAGE]].<ref>{{cite journal | vauthors = Penumutchu SR, Chou RH, Yu C | title = Structural insights into calcium-bound S100P and the V domain of the RAGE complex | journal = PLOS ONE | volume = 9 | issue = 8 | pages = e103947 | date = 2014-08-01 | pmid = 25084534 | pmc = 4118983 | doi = 10.1371/journal.pone.0103947 | doi-access = free | bibcode = 2014PLoSO...9j3947P }}</ref><ref>{{cite journal | vauthors = Penumutchu SR, Chou RH, Yu C | title = Interaction between S100P and the anti-allergy drug cromolyn | journal = Biochemical and Biophysical Research Communications | volume = 454 | issue = 3 | pages = 404–409 | date = November 2014 | pmid = 25450399 | doi = 10.1016/j.bbrc.2014.10.048 }}</ref>

==Synthesis==

[[File:Cromoglicic acid synthesis.svg|alt=Cromoglicic acid synthesis.|'''Cromoglicic acid synthesis'''.]]

==See also==

[[Visnaga daucoides]]

== References ==

{{reflist}}

== External links ==

[[Category:Enoic acids]]

[[Category:British inventions]]

[[Category:Glycerols]]

[[Category:Orphan drugs]]