Browse history interactively

Page 1

Page 1Revision 1

Page 2

Page 2Revision 2

← Previous editContent deleted Content addedVisualWikitext

Revision as of 09:18, 31 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit		Latest revision as of 14:42, 25 August 2024 edit undoIntentionallyDense (talk | contribs)Extended confirmed users, New page reviewers34,444 edits →History
(126 intermediate revisions by 85 users not shown)
Line 1:		Line 1:
			{{Short description|Chemical compound}}
	{{Drugbox
			{{cs1 config|name-list-style=vanc}}
			{{Infobox drug
	| Verifiedfields = changed		| Verifiedfields = changed
	| verifiedrevid = 396319029		| verifiedrevid = 458268085
	| IUPAC_name = 5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4''H''-chromene-2-carboxylic acid)		| IUPAC_name = 5,5′-(2-hydroxypropane-1,3-diyl)bis(oxy)bis(4-oxo-4''H''-chromene-2-carboxylic acid)
	| image = Cromoglicic acid.svg		| image = Cromoglicic acid.svg
			| image2 = Cromolyn ball-and-stick animation.gif
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename =
	| Drugs.com = {{drugs.com|international|cromoglicic-acid}}		| Drugs.com = {{drugs.com|international|cromoglicic-acid}}
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = B1
		⚫	| pregnancy_category =
	| pregnancy_US = <!-- A / B / C / D / X -->
			| legal_AU = S2
⚫	| pregnancy_category = B
	| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
	| legal_CA =		| legal_CA =
			| legal_UK_comment = inhaler POM; eye OTC
	| legal_UK = <!-- see expanded description below -->
	| legal_US = <!-- OTC / Rx-only -->		| legal_US = OTC
			| legal_US_comment = nasal; eye, inhaler: Rx only<!-- OTC / Rx-only -->
	| legal_status = inhaler POM, eye OTC<small>(])</small> nasal OTC, eye, inhaler Rx<small>(])</small>
			| licence_US = Cromolyn
			| legal_status =
	| routes_of_administration = topical: oral, nasal spray, inhaled, eye drops		| routes_of_administration = topical: oral, nasal spray, inhaled, eye drops
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = 1%		| bioavailability = 1%
Line 23:		Line 25:
	| metabolism =		| metabolism =
	| elimination_half-life = 1.3 hours		| elimination_half-life = 1.3 hours
	| excretion =		| excretion =
	<!--Identifiers-->		<!--Identifiers-->
			| IUPHAR_ligand = 7608
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 16110-51-3		| CAS_number = 16110-51-3
Line 33:		Line 34:
	| ATC_supplemental = {{ATC|D11|AH03}} {{ATC|R01|AC01}} {{ATC|R03|BC01}} {{ATC|S01|GX01}}		| ATC_supplemental = {{ATC|D11|AH03}} {{ATC|R01|AC01}} {{ATC|R03|BC01}} {{ATC|S01|GX01}}
	| PubChem = 2882		| PubChem = 2882
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
	| DrugBank = <!-- blanked - oldvalue: APRD00336 -->		| DrugBank = DB01003
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 2779		| ChemSpiderID = 2779
	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = Y0TK0FS77W		| UNII = Y0TK0FS77W
	| KEGG_Ref = {{keggcite|changed|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D07753		| KEGG = D07753
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 59773		| ChEBI = 59773
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| ChEMBL = <!-- blanked - oldvalue: 74 -->		| ChEMBL = 74
			<!--Chemical data-->
	| C=23 | H=16 | O=11		| C=23 | H=16 | O=11
	| molecular_weight = 468.367 g/mol
	| smiles = O=C(O)C=4Oc3cccc(OCC(O)COc2cccc1O/C(=C\C(=O)c12)C(=O)O)c3C(=O)C=4		| smiles = O=C(O)C=4Oc3cccc(OCC(O)COc2cccc1O/C(=C\C(=O)c12)C(=O)O)c3C(=O)C=4
	| InChI = 1/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)
	| InChIKey = IMZMKUWMOSJXDT-UHFFFAOYAY
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 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)		| StdInChI = 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)
Line 55:		Line 54:
	| StdInChIKey = IMZMKUWMOSJXDT-UHFFFAOYSA-N		| StdInChIKey = IMZMKUWMOSJXDT-UHFFFAOYSA-N
	}}		}}
⚫	'''Cromoglicic acid''' (]) (also referred to as '''cromolyn''' (]), '''cromoglycate''' (former ]), or '''cromoglicate''') is traditionally described as a ], and is commonly marketed as the sodium salt '''sodium cromoglicate''' or '''cromolyn sodium'''. This drug prevents the release of ] chemicals such as ] from ]s.
		⚫	'''Cromoglicic acid''' (])—also referred to as '''cromolyn''' (]), '''cromoglycate''' (former ]), or '''cromoglicate'''—is traditionally described as a ], and is commonly marketed as the sodium salt '''sodium cromoglicate''' or '''cromolyn sodium'''. This drug prevents the release of ] chemicals such as ] from ]s.
⚫	Because of their convenience (and perceived safety), ]s have largely replaced it as the non-] treatment of choice in the treatment of ]. Cromoglicic acid requires administration four times daily, and does not provide additive benefit in combination with inhaled corticosteroids.<ref>{{cite journal |author=Fanta CH |title=Asthma |journal=] |volume=360 |issue=10 |pages=1002–14 |year=2009 |month=March |pmid=19264689 |doi=10.1056/NEJMra0804579}} Review.</ref>
			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-] treatment of choice in the treatment of ], for which it has largely been replaced by ]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>
	==History==		==History==
	Cromolyn sodium was discovered by Dr. ] 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 ] (''Ammi visnaga'') which had been used as a muscle relaxant since ancient times in Egypt. Dr. Altounyan deliberately inhaled derivatives of the active ingredient ] 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.		Cromolyn was discovered in 1965 by ], a ] who had asthma. Altounyan was investigating certain plants and herbs which have bronchodilating properties. One such plant was ] (''Ammi visnaga'') which had been used as a muscle relaxant since ancient times in Egypt. Altounyan deliberately inhaled derivatives of the active ingredient ] 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>
	==Preparations==		==Preparations==
	Cromoglicic acid is available in multiple forms:		Cromoglicic acid is available in multiple forms:
	* as a ] (Rynacrom(UK), Nasalcrom, Prevalin (Netherlands)) to treat ].		* as a ] (Rynacrom (UK), Lomusol (France), Nasalcrom (the only ] form, US), Prevalin (non-direct version, NL)) to treat ].
	* in a nebulizer solution for aerosol administration to treat ].		* in a nebulizer solution for aerosol administration to treat ].
		⚫	* as an ] (Intal, Fisons Pharmaceuticals, UK) for preventive management of ].<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 ], although it must be imported from Canada or Mexico for USA residents.
			* as ]s (Opticrom and Optrex Allergy (UK), Crolom, Cromolyn (Canada)) for ]<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>
⚫	* as an ] (Intal) for preventive management of ].<ref name="pmid8635375">{{cite journal |author=Schwartz HJ, Blumenthal M, Brady R, ''et al.'' |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=945–52 |year=1996 |month=April |pmid=8635375 |doi= 10.1378/chest.109.4.945|url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=8635375}}</ref> 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.<ref>http://www.empr.com/Intal-Inhaler-discontinued/article/141142/</ref> In the EU it is manufactured without CFCs by Sanofi-Aventis, although it must be imported from Canada for USA residents.
		⚫	* in an oral form (Gastrocrom, Nalcrom) to treat ],<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> ], ] and ]. Another oral product, Intercron (sodium cromoglicate in distilled water, from ] France), is used for food allergies.
	* as ]s (Opticrom and Optrex Allergy (UK), Crolom) for ]
⚫	* in an oral form (Gastrocrom) to treat ],<ref name="pmid2110198">{{cite journal |doi=10.1016/0091-6749(90)90067-E |author=Horan RF, Sheffer AL, Austen KF |title=Cromolyn sodium in the management of systemic mastocytosis |journal=J. Allergy Clin. Immunol. |volume=85 |issue=5 |pages=852–5 |year=1990 |month=May |pmid=2110198 }}</ref> ] and ]. Another oral product, Intercron (sodium cromoglicate in distilled water, from ] France), is used for food allergies.
	==Mechanism of action==		==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."<ref>Werner's Pathophysiology page 224</ref> ] is another mast cell stabilizer that also works in controlling asthma.		"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> ] is another mast cell stabilizer that also works in controlling asthma.
	The underlying ] is not fully understood; for while cromoglicate stabilizes mast cells, this mechanism is probably not why it works in asthma.<ref name="rang">H. P. Rang et al., ''Pharmacology'', Fifth Edition. (2003) ISBN 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 ]s to the irritant ], 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)		The underlying ] 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 ] to the irritant ], 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 ] (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:
	It is known to somewhat inhibit ] (37% +/- 7%) <ref>{{cite journal
	| quotes =
	| first = S
	| last = Heinke
	| coauthors = Szucs G, Norris A, Droogmans G, Nilius B
	| year = 1995
	| month = August
	| title = Inhibition of volume-activated chloride currents in endothelial cells by chromones
	| journal = Br J Pharmacol.
	| volume = 115
	| pages = 1393–8
	| pmid = 8564197
	| issue = 8
	| pmc = 1908889
	}}</ref> and thus ''may'' inhibit the:
	* exaggerated neuronal reflexes triggered by stimulation of irritant receptors on sensory nerve endings (e.g. exercise-induced asthma)		* exaggerated neuronal reflexes triggered by stimulation of irritant receptors on sensory nerve endings (e.g. exercise-induced asthma)
	* release of preformed ] from several type of inflammatory cells (]s, ]) in allergen-induced asthma		* release of preformed ] from several type of inflammatory cells (]s, ]) in allergen-induced asthma
Line 103:		Line 87:
	Cromoglicate is classified as a ].		Cromoglicate is classified as a ].
			Cromolyn is also being tested as a drug to treat ]<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 ] in combination with ].<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 ].<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>
⚫	==References==
⚫	{{reflist|2}}
			==Synthesis==
			]
			==See also==
			]
		⚫	== References ==
		⚫	{{reflist}}
			== External links ==
	{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}		{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
	{{Other dermatological preparations}}		{{Other dermatological preparations}}
Line 112:		Line 107:
	]		]
	]		]
⚫	]
	]		]
			]
			]
	]
		⚫	]
	]
	]
	]
	]
	]
	]
	]
	]