| Revision as of 12:13, 24 November 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456685202 of page Methoxsalen for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 00:28, 16 October 2024 edit Schubladenzieher (talk | contribs)13 editsm Correction of the IUPAC name.Tag: Visual edit |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Drugbox |
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{{Drugbox |
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| verifiedrevid = 462250014 |
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| Verifiedfields = changed |
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| verifiedrevid = 420095250 |
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| IUPAC_name = 9-methoxy-7''H''-furochromen-7-one |
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| image = Methoxsalen.svg |
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| image = Methoxsalen.svg |
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| alt = <!-- Clinical data --> |
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| pronounce = |
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<!--Clinical data--> |
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| tradename = |
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| tradename = Oxsoralen, Uvadex, 8-mop, others |
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| Drugs.com = {{drugs.com|CDI|methoxsalen}} |
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| Drugs.com = {{drugs.com|CDI|methoxsalen}} |
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| MedlinePlus = |
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| DailyMedID = Methoxsalen |
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| pregnancy_AU = D |
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| pregnancy_AU_comment = <ref name="Uvadex APM summary">{{cite web | title=Uvadex | website=] (TGA) | date=13 December 2019 | url=https://www.tga.gov.au/resources/auspmd/uvadex | access-date=25 August 2020}}</ref><ref name="AusPAR: Methoxsalen">{{cite web | title=AusPAR: Methoxsalen | website=Therapeutic Goods Administration (TGA) | date=12 December 2019 | url=https://www.tga.gov.au/auspar/auspar-methoxsalen | access-date=17 September 2021}}</ref> |
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| pregnancy_category = |
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| routes_of_administration = Extracorporeal, ] |
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| class = |
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| ATC_prefix = D05 |
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| ATC_suffix = AD02 |
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| ATC_supplemental = {{ATC|D05|BA02}} |
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<!-- Legal status -->| legal_AU = S4 |
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<!--Pharmacokinetic data--> |
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| legal_AU_comment = <ref name="Uvadex APM summary" /><ref name="AusPAR: Methoxsalen" /> |
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| elimination_half-life = ~2 hours |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Uvadex FDA label">{{cite web | title=Uvadex- methoxsalen injection, solution | website=DailyMed | publisher = U.S. National Library of Medicine | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ad333bd-845f-43f8-9ecf-43491f26c7c7 | access-date=17 September 2021 }}</ref><ref>{{cite web | title=Oxsoralen-Ultra- methoxsalen capsule, liquid filled | website=DailyMed | publisher = U.S. National Library of Medicine | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ae951dc4-9031-43bf-943c-cb2366951f23 | access-date=17 September 2021}}</ref> |
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| legal_EU = |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = <!-- For countries not listed above --> |
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<!-- Pharmacokinetic data -->| bioavailability = |
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<!--Identifiers--> |
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| protein_bound = |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| metabolism = |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| metabolites = |
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| onset = |
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| elimination_half-life = ~2 hours |
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| duration_of_action = |
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| excretion = <!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| CAS_number = 298-81-7 |
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| CAS_number = 298-81-7 |
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| ATC_prefix = D05 |
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| ATC_suffix = AD02 |
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| ATC_supplemental = {{ATC|D05|BA02}} |
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| PubChem = 4114 |
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| PubChem = 4114 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 3971 |
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| ChemSpiderID = 3971 |
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| NIAID_ChemDB = 001590 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = U4VJ29L7BQ |
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| UNII = U4VJ29L7BQ |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00139 |
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| KEGG = D00139 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 18358 |
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| ChEBI = 18358 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 416 |
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| ChEMBL = 416 |
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| synonyms = xanthotoxin |
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<!-- Chemical and physical data -->| IUPAC_name = 9-methoxy-7''H''-furobenzopyran-7-one |
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<!--Chemical data--> |
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| C=12 | H=8 | O=4 |
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| C = 12 |
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| H = 8 |
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| molecular_weight = 216.19 g/mol |
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| O = 4 |
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| smiles = COc1c2c(ccc(=O)o2)cc3c1occ3 |
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| smiles = COc1c2c(ccc(=O)o2)cc3c1occ3 |
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| InChI = 1/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3 |
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| InChIKey = QXKHYNVANLEOEG-UHFFFAOYAV |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3 |
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| StdInChI = 1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3 |
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| StdInChIKey = QXKHYNVANLEOEG-UHFFFAOYSA-N |
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| StdInChIKey = QXKHYNVANLEOEG-UHFFFAOYSA-N |
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}} |
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}} |
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'''Methoxsalen''' (or '''Xanthotoxin''', '''8-methoxypsoralen''') sold under the brand name '''Oxsoralen''' among others, is a ] used to treat ], ], ], and some ] in conjunction with exposing the skin to ] (UVA) light from lamps or sunlight. Methoxsalen modifies the way skin cells receive the UVA radiation, allegedly clearing up the disease. Levels of individual patient PUVA exposure were originally determined using the ]. The scale was developed after patients demonstrated symptoms of ] after oral ingestion of methoxsalen followed by PUVA therapy. |
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Chemically, methoxsalen is a derivative of ] and belongs to a class of organic natural molecules known as ]s. They consist of ] ]d with ]. It can also be injected and used topically. |
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== Natural sources == |
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In 1947, methoxsalen was isolated (under the name "ammoidin") from the plant '']'', bishop's weed.<ref>{{cite journal | vauthors = Fahmy IR, Abu-Shady H | title = Ammi majus Linn.; pharmacognostical study and isolation of a crystalline constituent, ammoidin | journal = Quarterly Journal of Pharmacy and Pharmacology | volume = 20 | issue = 3 | pages = 281–91; discussion 426 | year = 1947 | pmid = 20273299 }}</ref><ref name="Marshall-2006">{{cite journal | vauthors = Marshall SR | title = Technology insight: ECP for the treatment of GvHD--can we offer selective immune control without generalized immunosuppression? | journal = Nature Clinical Practice. Oncology | volume = 3 | issue = 6 | pages = 302–314 | date = June 2006 | pmid = 16757968 | doi = 10.1038/ncponc0511 | publisher = ] | s2cid = 8441159 }}</ref> |
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In 1970, Nielsen extracted 8-methoxypsoralen from four species of the genus '']'' in the carrot family ],<ref>{{cite book | vauthors = Nielsen BE |title=Coumarins of Umbelliferous plants |date=1970 |publisher=Royal Danish School of Pharmacy |location=Copenhagen}} Cited by Mitchell and Rook (1979).</ref><ref>{{cite book | vauthors = Mitchell J, Rook A |title=Botanical Dermatology: Plants and Plant Products Injurious to the Skin |date=1979 |publisher=Greengrass |location=Vancouver |pages=692–699 | isbn = 978-0-88978-047-7 }}</ref> including '']'' and '']''. An additional 32 species of the genus ''Heracleum'' were found to contain 5-methoxypsoralen (]) or other ]s. |
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== Biosynthesis == |
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The biosynthetic pathway is a combination of the ] pathway, which produces ], and the ]. |
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=== Synthesis of umbelliferone === |
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Umbelliferone is a ] and as such is synthesized from ], which in turn is produced via the shikimate pathway. Phenylalanine is lysated into ], followed by ] by ] to yield ]. The 4-coumaric acid is again hydroxylated by cinnamate/coumarate 2-hydroxylase to yield 2,4-dihydroxy-cinnamic acid (]) followed by a bond rotation of the unsaturated bond adjacent to the ] group. Finally an intramolecular attack from the hydroxyl group of C2' to the carboxylic acid group closes the ring and forms the ] umbelliferone. |
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=== Synthesis of methoxsalen === |
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]]] |
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The biosynthetic route then continues with the activation of ] (DMAPP), produced via the mevalonate pathway, to form a carbo-cation via the cleavage of the diphosphates. Once activated, the enzyme umbelliferone 6-prenyltransferase catalyzes a C-alkylation between DMAPP and umbelliferone at the activated position ortho to the phenol, yielding demethylsuberosin. This is then followed by a hydroxylation catalyzed by the enzyme marmesin synthase to yield ]. Another hydroxylation is catalyzed by ] to yield ]. A third hydroxylation by the enzyme psoralen 8-monooxygenase yields xanthotoxol which is followed by a methylation via the enzyme ] and ] to yield methoxsalen.<ref>{{cite book| vauthors = Dewick PM |title=Medicinal Natural Products: A Biosynthetic Approach|edition=3rd|publisher=John Wiley & Sons|year=2009|pages=161, 164–165}}</ref> |
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== Risks and side effects == |
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Patients with ] or a history of ] problems are at risk for inflammation and irreparable damage to both liver and skin. The eyes must be protected from UVA radiation. Side effects include ], ]s, ], and in rare cases ]. |
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Methoxsalen has also been classified as an ] (known to cause cancer) but is only cancerous when combined with light - UVA radiation.<ref>{{cite web | title = Known and Probable Human Carcinogens | url = http://www.cancer.org/cancer/cancercauses/othercarcinogens/generalinformationaboutcarcinogens/known-and-probable-human-carcinogens | archive-url = https://web.archive.org/web/20160930103933/http://www.cancer.org/cancer/cancercauses/othercarcinogens/generalinformationaboutcarcinogens/known-and-probable-human-carcinogens | archive-date= 30 September 2016 | publisher = American Cancer Society }}</ref> |
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== Society and culture == |
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Author ] (1920–1980) used the chemical to darken his skin in order to investigate racial segregation in the American South. He wrote the book '']'' (1961) about his experiences.<ref>{{cite web | vauthors = Mikkelson D | date = 27 July 2003 | url = http://www.snopes.com/horrors/freakish/griffin.asp | title = Death of John Howard Griffin | work = snopes.com | publisher = Snopes Media Group Inc. }}</ref> |
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== References == |
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{{reflist}} |
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{{Antipsoriatics}} |
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{{Coumarin}} |
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{{Portal bar | Medicine}} |
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