Doxylamine

Doxylamine
Clinical data
Trade names	Unisom, Vicks Formula 44 (in combination with Dextromethorphan), others
AHFS/Drugs.com	Monograph
MedlinePlus	a682537
Pregnancy; category	AU: A; A (Briggs);
Routes of; administration	By mouth
ATC code	R06AA09 (WHO) ;
Legal status
Legal status	AU: S3 (Pharmacist only); US: OTC;
Pharmacokinetic data
Bioavailability	Oral: 24.7%; Intranasal: 70.8%
Metabolism	Hepatic (CYP2D6, CYP1A2, CYP2C9)
Elimination half-life	10–12 hours (range 7–15 hours)
Excretion	Urine (60%), feces (40%)
Identifiers
	IUPAC name (RS)-N,N-dimethyl-2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethan-1-amine;
CAS Number	469-21-6 ;
PubChem CID	3162;
IUPHAR/BPS	7171;
DrugBank	DB00366 ;
ChemSpider	3050 ;
UNII	95QB77JKPL;
KEGG	D07878 ;
ChEBI	CHEBI:51380 ;
ChEMBL	ChEMBL1004 ;
CompTox Dashboard (EPA)	DTXSID1022970 ;
ECHA InfoCard	100.006.742
Chemical and physical data
Formula	C17H22N2O
Molar mass	270.376 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES n1ccccc1C(c1ccccc1)(C)OCCN(C)C;
	InChI InChI=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 ; Key:HCFDWZZGGLSKEP-UHFFFAOYSA-N ;
	(verify)

Doxylamine is an antihistamine medication used to treat insomnia and allergies, and—in combination with pyridoxine (vitamin B₆)—to treat morning sickness in pregnant women. It is available over-the-counter and is typically sold under such brand names as Equate, Unisom, or ZzzQuil, among others; and it is used in nighttime cold medicines (e.g., NyQuil) and pain medications containing acetaminophen and/or codeine to help with sleep. The medication is delivered chemically by the salt doxylamine succinate and is taken by mouth. Doxylamine and other first-generation antihistamines are the most widely used sleep medications in the world.^[6]Typical side effects of doxylamine (at recommended doses) include dizziness, drowsiness, grogginess, and dry mouth, among others.^[7]^[4]

As an antihistamine, doxylamine is an inverse agonist of the histamine H₁ 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. (N.b.: An agonist is a molecule that activates certain receptors (i.e., specific cellular proteins} in a cell to produce a specific pharmacological response, causing the cell to modify its activity—while an inverse agonist targets the same receptors as those of a given agonist, but causes a response opposite to that caused by the agonist. An antagonist blocks the action of a given agonist.)

Doxylamine is also a potent anticholinergic, meaning that it causes delium at high doses—i.e., at much higher doses than recommended.^[8] (Specifically it is an antagonist of the muscarinic acetylcholine receptors M₁ through M₅.) These sedative and deliriant effects have in some cases led to using the drug recreationally. Doxylamine was first described in 1948 or 1949.^[9]

^ ^a ^b Cite error: The named reference pmid12214324 was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference KrygerRoth2010 was invoked but never defined (see the help page).
^ Cite error: The named reference pmid29671128 was invoked but never defined (see the help page).
^ ^a ^b Cite error: The named reference pmid27057416 was invoked but never defined (see the help page).
^ "New Zealand Datasheet: Doxylamine Succinate" (PDF). Medsafe, New Zealand Medicines and Medical Devices Safety Authority. 16 July 2008. Archived from the original on 22 March 2016.
^ Cite error: The named reference SimonsSimons2011 was invoked but never defined (see the help page).
^ Neubauer DN (August 2007). "The evolution and development of insomnia pharmacotherapies". Journal of Clinical Sleep Medicine. 3 (5 Suppl): S11–S15. doi:10.5664/jcsm.26930. PMC 1978321. PMID 17824496.
^ "Doxylamine - PsychonautWiki".
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.

[pmid12214324-1] Cite error: The named reference pmid12214324 was invoked but never defined (see the help page).

[KrygerRoth2010-2] Cite error: The named reference KrygerRoth2010 was invoked but never defined (see the help page).

[pmid29671128-3] Cite error: The named reference pmid29671128 was invoked but never defined (see the help page).

[pmid27057416-4] Cite error: The named reference pmid27057416 was invoked but never defined (see the help page).

[NZlabel-5] "New Zealand Datasheet: Doxylamine Succinate" (PDF). Medsafe, New Zealand Medicines and Medical Devices Safety Authority. 16 July 2008. Archived from the original on 22 March 2016.

[SimonsSimons2011-6] Cite error: The named reference SimonsSimons2011 was invoked but never defined (see the help page).

[pmid17824496-7] Neubauer DN (August 2007). "The evolution and development of insomnia pharmacotherapies". Journal of Clinical Sleep Medicine. 3 (5 Suppl): S11–S15. doi:10.5664/jcsm.26930. PMC 1978321. PMID 17824496.

[8] "Doxylamine - PsychonautWiki".

[Fis2006-9] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 546. ISBN 9783527607495.

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