Editing Doxylamine (section)

{{Short description|First-generation antihistamine used as a short-term sedative and hypnotic (sleep aid)}}
{{Use dmy dates|date=April 2023}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 456483386
| IUPAC_name = (''RS'')-''N'',''N''-dimethyl-2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethan-1-amine
| image = Doxylamine structure.svg
| image_class = skin-invert-image
| width = 200px
| alt = Skeletal formula of the doxylamine molecule
| image2 = Doxylamine 3D ball.png
| width2 = 200px
| alt2 = Ball-and-stick model of the doxylamine molecule

<!--Clinical data-->
| tradename = Unisom, [[Vicks]] Formula 44 (in combination with [[Dextromethorphan]]), others
| Drugs.com = {{drugs.com|monograph|doxylamine-succinate}}
| MedlinePlus = a682537
| pregnancy_US = B
| pregnancy_AU = A
| pregnancy_category = A (Briggs)
| legal_AU = S3
| legal_US = OTC
| routes_of_administration = [[Oral administration|By mouth]]

<!--Pharmacokinetic data-->
| bioavailability = [[Oral administration|Oral]]: 24.7%<ref name=pmid12214324/><br/>[[Intranasal administration|Intranasal]]: 70.8%<ref name=pmid12214324/>
| metabolism = [[Liver|Hepatic]] ([[CYP2D6]], [[CYP1A2]], [[CYP2C9]])<ref name=KrygerRoth2010/>
| elimination_half-life = 10–12 hours (range 7–15 hours)<ref name="KrygerRoth2010" /><ref name="pmid29671128" /><ref name="pmid27057416" />
| excretion = [[Urine]] (60%), [[feces]] (40%)<ref name=NZlabel>{{cite web|title=New Zealand Datasheet: Doxylamine Succinate|url=http://www.medsafe.govt.nz/profs/datasheet/d/Dozilecap.pd|publisher=Medsafe, New Zealand Medicines and Medical Devices Safety Authority|archive-url=https://web.archive.org/web/20160322211016/http://www.medsafe.govt.nz/profs/datasheet/d/Dozilecap.pdf|archive-date=22 March 2016|date=16 July 2008|url-status=dead}}</ref>

<!--Identifiers-->
| IUPHAR_ligand = 7171
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 469-21-6
| ATC_prefix = R06
| ATC_suffix = AA09
| PubChem = 3162
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00366
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 3050
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 95QB77JKPL
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07878
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 51380
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1004
| synonyms =

<!--Chemical data-->
| C=17 | H=22 | N=2 | O=1
| SMILES = n1ccccc1C(c1ccccc1)(C)OCCN(C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C17H22N2O/c1-17(20-14-13-19(2)3,15-9-5-4-6-10-15)16-11-7-8-12-18-16/h4-12H,13-14H2,1-3H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HCFDWZZGGLSKEP-UHFFFAOYSA-N
}}
'''Doxylamine''' is an [[antihistamine]] medication used to treat [[insomnia]] and [[allergy|allergies]], and—in combination with [[pyridoxine]] ([[vitamin B6|vitamin B<sub>6</sub>]])—to treat [[morning sickness]] in [[pregnant]] women. It is available [[over-the-counter]] and is sold under such brand names as '''Equate''' or '''Unisom''', among others; and it is used in nighttime [[cold medicine]]s (e.g., [[NyQuil]]) and [[pain medication]]s containing [[paracetamol]] (acetaminophen) or [[codeine]] to help with [[sleep]]. The medication is delivered chemically by the salt doxylamine succinate and is taken [[oral administration|by mouth]]. Doxylamine and other [[first-generation antihistamine]]s are the most widely used sleep medications in the world.<ref name="SimonsSimons2011" /> Typical [[side effect]]s of doxylamine include [[dizziness]], [[drowsiness]], [[grogginess]], and [[dry mouth]], among others.<ref name="pmid17824496">{{cite journal | vauthors = Neubauer DN | title = The evolution and development of insomnia pharmacotherapies | journal = Journal of Clinical Sleep Medicine | volume = 3 | issue = 5 Suppl | pages = S11–S15 | date = August 2007 | pmid = 17824496 | pmc = 1978321 | doi = 10.5664/jcsm.26930 }}</ref><ref name="pmid27057416" /> 

As an antihistamine, doxylamine is an [[inverse agonist]] of the [[histamine]] [[H1 receptor|H<sub>1</sub> receptor]]. As a first-generation antihistamine, it typically crosses the [[blood–brain barrier]] into the [[brain]], thereby producing a suite of [[sedative]] and [[hypnotic]] effects that are mediated by the [[central nervous system]].  

Doxylamine is also a potent [[anticholinergic]], meaning that it [[deliriant|causes delirum]] at high doses (i.e., at much higher doses than recommended).<ref>{{cite web | url=https://psychonautwiki.org/wiki/Doxylamine | title=Doxylamine - PsychonautWiki }}</ref> Specifically, it is an [[receptor antagonist|antagonist]] of the [[muscarinic acetylcholine receptor]]s [[muscarinic acetylcholine receptor M1|M<sub>1</sub>]] through [[muscarinic acetylcholine receptor M5|M<sub>5</sub>]]. These sedative and deliriant effects have in some cases led to the drug being used recreationally. Doxylamine was first described in 1948 or 1949.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=546 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA546 }}</ref>