Histamine H1 antagonist with pronounced sedative properties. It is used in allergies and as an antitussive, antiemetic, and hypnotic. Doxylamine has also been administered in veterinary applications and was formerly used in parkinsonism.

Structure

Similar Structures

Synonyms

2-(alpha-(2-(Dimethylamino)ethoxy)-alpha-methylbenzyl)pyridine
2-Dimethylaminoethoxyphenylmethyl-2-picoline
Dossilamina
Doxilamina
Doxilminio
Doxylamine
Doxylaminum
N,N-Dimethyl-2-(1-phenyl-1-(2-pyridinyl)ethoxy)ethanamine
Phenyl-2-pyridylmethyl-beta-N,N-dimethylaminoethyl ether

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Doxylamine succinate	V9BI9B5YI2	562-10-7	KBAUFVUYFNWQFM-UHFFFAOYSA-N

Product Images

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
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7 Select Sleep Aid	Tablet	25 mg/1	Oral	7-Eleven	2014-08-05	2022-02-28
Aldex AN	Tablet, chewable	5 mg/1	Oral	Pernix Therapeutics	2010-01-20	2012-10-31
Basic Care Sleep Aid	Tablet	25 mg/1	Oral	L. Perrigo Company	2018-03-06	Not applicable
Berkley and Jensen Sleep Aid	Tablet	25 mg/1	Oral	BJWC	2018-08-06	Not applicable
Care One Sleep Aid	Tablet	25 mg/1	Oral	American Sales Company	2004-06-29	2018-12-01
CareOne Nighttime Sleep Aid	Tablet	25 mg/1	Oral	American Sales Company	2016-05-06	Not applicable
Equaline Sleep Aid	Tablet	25 mg/1	Oral	Supervalu	2004-08-10	2015-11-01
Equate sleep aid	Tablet	25 mg/1	Oral	Walmart Stores	1997-02-25	2014-01-27
Good Neighbor Pharmacy Sleep Aid	Tablet	25 mg/1	Oral	Amerisource Bergen	1997-06-26	Not applicable
Good sense sleep aid	Tablet	25 mg/1	Oral	L. Perrigo Company	1997-04-14	Not applicable

Additional Data Available

Application Number

A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
7 Select Night Time Relief	Doxylamine succinate (12.5 mg/30mL) + Acetaminophen (650 mg/30mL) + Dextromethorphan hydrobromide monohydrate (30 mg/30mL)	Solution	Oral	7-Eleven	2014-08-05	2021-03-31
7 Select Night Time Relief	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)	Capsule, liquid filled	Oral	7-Eleven	2014-04-17	2020-07-31
Acetaminophen Dextromethorphan HBr Doxylamine succinate Phenylephrine HCl	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)	Capsule, liquid filled	Oral	Cvs Pharmacy,inc	2017-07-07	Not applicable
Acetaminophen Dextromethorphan HBr Doxylamine succinate Phenylephrine HCl	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)	Capsule, liquid filled	Oral	CVS Health	2017-11-30	Not applicable
ACETAMINOPHEN DEXTROMETHORPHAN HYDROBROMIDE and DOXYLAMINE SUCCINATE	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)	Capsule, liquid filled	Oral	J.P. BUSINESS ENTERPRISE	2014-12-01	Not applicable
Acetaminophen Dextromethorphan Hydrobromide Doxylamine Succinate Phenylephrine hydrochloride	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)	Capsule, liquid filled	Oral	Healthlife of Usa	2017-07-07	2017-07-07
Acetaminophen Dextromethorphan Hydrobromide Doxylamine Succinate Phenylephrine Hydrochloride	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)	Capsule, liquid filled	Oral	Granules India Limited	2017-07-07	Not applicable
ACETAMINOPHEN, DEXTROMETHORPHAN HYDROBROMIDE, and DOXYLAMINE SUCCINATE	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)	Capsule, liquid filled	Oral	Spirit Pharmaceuticals, Llc	2009-10-15	Not applicable
Acetaminophen,Dextromethorphan,Doxylamine	Doxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1)	Capsule, liquid filled	Oral	Agile Pharmachem	2014-05-01	Not applicable
Acetaminophen/pseudoephedrine/dextromethorphan/doxylamine	Doxylamine succinate (6.25 mg) + Acetaminophen (325 mg) + Dextromethorphan hydrobromide (15 mg) + Pseudoephedrine hydrochloride (30 mg)	Capsule	Oral	Apotex Corporation	Not applicable	Not applicable

Categories

UNII

95QB77JKPL

CAS number

469-21-6

Weight

Average: 270.3694
Monoisotopic: 270.173213336

Chemical Formula

C₁₇H₂₂N₂O

InChI Key

HCFDWZZGGLSKEP-UHFFFAOYSA-N

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

IUPAC Name

dimethyl({2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethyl})amine

SMILES

CN(C)CCOC(C)(C1=CC=CC=C1)C1=CC=CC=N1

Pharmacology

Indication

Used alone as a short-term sleep aid, in combination with other drugs as a night-time cold and allergy relief drug. Also used in combination with Vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.

Associated Conditions

Pharmacodynamics

Doxylamine is an antihistamine commonly used as a sleep aid. This drug is also used to relieve symptoms of hay fever (allergic rhinitis), hives (rash or itching), and other allergic reactions. Doxylamine is a member of the ethanolamine class of antihistamines and has anti-allergy power far superior to virtually every other antihistamine on the market, with the exception of diphenhydramine (Benadryl). It is also the most powerful over-the-counter sedative available in the United States, and more sedating than many prescription hypnotics. In a study, it was found to be superior to even the barbiturate, phenobarbital for use as a sedative. Doxylamine is also a potent anticholinergic.

Mechanism of action

Like other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.

Target	Actions	Organism
AHistamine H1 receptor	antagonist	Humans
UMuscarinic acetylcholine receptor M1	antagonist	Humans
UNuclear receptor subfamily 1 group I member 3	Not Available	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Readily absorbed via the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic.

Route of elimination

Not Available

Half life

10 hours

Clearance

Not Available

Toxicity

Signs of overdose include wheezing, tightness in the chest, fever, itching, bad cough, blue skin color, fits, swelling of face, lips, tongue, or throat.

Affected organisms

Humans and other mammals

Pathways

Pathway	Category
Doxylamine H1-Antihistamine Action	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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1,10-Phenanthroline	The therapeutic efficacy of Doxylamine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine	2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Doxylamine.
2,5-Dimethoxy-4-ethylthioamphetamine	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
4-Bromo-2,5-dimethoxyamphetamine	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-Methoxyamphetamine	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamine	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 5-methoxy-N,N-dimethyltryptamine.
7-Nitroindazole	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline	Doxylamine may increase the central nervous system depressant (CNS depressant) activities of 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Abediterol	The risk or severity of Tachycardia can be increased when Doxylamine is combined with Abediterol.
Abexinostat	The risk or severity of QTc prolongation can be increased when Doxylamine is combined with Abexinostat.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

References

General References

Not Available

External Links

Human Metabolome Database: HMDB0001936
KEGG Drug: D02327
PubChem Compound: 3162
PubChem Substance: 46506354
ChemSpider: 3050
BindingDB: 50239996
ChEBI: 51380
ChEMBL: CHEMBL1004
Therapeutic Targets Database: DAP000859
PharmGKB: PA449419
Drugs.com: Drugs.com Drug Page
Wikipedia: Doxylamine

ATC Codes

R06AA09 — Doxylamine

R06AA59 — Doxylamine, combinations

AHFS Codes

04:04.04 — Ethanolamine Derivatives

MSDS

Download (74 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
1	Completed	Not Available	Allergic Rhinitis (AR) / Upper Respiratory Tract Infection	1
1	Withdrawn	Treatment	Bioavailability	1
3	Completed	Prevention	Hyperemesis Gravidarum / Pregnancy	1
3	Completed	Treatment	Herpes Simplex Labialis	1
3	Completed	Treatment	Nausea and Vomiting of Pregnancy	1
4	Recruiting	Treatment	Morning Sickness	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Amend
Centurion Labs
Chattem Chemicals Inc.
Deltex Pharmaceuticals Inc.
Duchesnay Inc.
Perrigo Co.

Dosage forms

Form	Route	Strength
Tablet, chewable	Oral	5 mg/1
Tablet, effervescent	Oral
Capsule	Not applicable
Tablet, extended release	Oral
Capsule; kit	Oral
Tablet	Oral
Kit	Oral
Tablet, delayed release	Oral
Syrup	Oral
Liquid	Oral
Solution	Oral
Capsule, liquid filled	Oral
Capsule	Oral
Capsule, gelatin coated	Oral
Tablet, coated	Oral
Syrup	Oral	9.75 mg/5mL
Tablet, film coated	Oral
Kit; tablet	Oral
Tablet	Oral	25 mg/1
Powder, for solution	Oral
Tablet	Oral

Prices

Unit description	Cost	Unit
Doxylamine succinate powder	1.5USD	g
Unisom sleep aid tablet	0.34USD	tablet
Sleep aid 25 mg tablet	0.15USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
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US6340695	No	2002-01-22	2021-06-21
US7560122	No	2009-07-14	2019-01-25
US9526703	No	2016-12-27	2033-02-18
US9375404	No	2016-06-28	2033-02-18
US9089489	No	2015-07-28	2033-02-18
US9937132	No	2018-04-10	2033-02-18

Additional Data Available

Filed On

The date on which a patent was filed with the relevant government.

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Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	< 25 °C	PhysProp
boiling point (°C)	139 °C at 5.00E-01 mm Hg	PhysProp
water solubility	1 g/ml (succinate salt)	Not Available
logP	2.5	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.541 mg/mL	ALOGPS
logP	2.9	ALOGPS
logP	2.96	ChemAxon
logS	-2.7	ALOGPS
pKa (Strongest Basic)	8.87	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	25.36 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	82.24 m³·mol^-1	ChemAxon
Polarizability	31.09 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9505
Blood Brain Barrier	+	0.9491
Caco-2 permeable	+	0.746
P-glycoprotein substrate	Substrate	0.7449
P-glycoprotein inhibitor I	Non-inhibitor	0.5123
P-glycoprotein inhibitor II	Non-inhibitor	0.8383
Renal organic cation transporter	Inhibitor	0.7507
CYP450 2C9 substrate	Non-substrate	0.8153
CYP450 2D6 substrate	Non-substrate	0.5432
CYP450 3A4 substrate	Substrate	0.6801
CYP450 1A2 substrate	Non-inhibitor	0.9092
CYP450 2C9 inhibitor	Non-inhibitor	0.8957
CYP450 2D6 inhibitor	Inhibitor	0.8361
CYP450 2C19 inhibitor	Non-inhibitor	0.8764
CYP450 3A4 inhibitor	Non-inhibitor	0.6894
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.736
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9183
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.9218 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8765
hERG inhibition (predictor II)	Inhibitor	0.5398

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-0ab9-9200000000-5a71de62862f9881c2a1
MS/MS Spectrum - Quattro_QQQ 10V, Positive	LC-MS/MS	splash10-0040-0956300000-af11cf85a674e7db3735
MS/MS Spectrum - Quattro_QQQ 25V, Positive	LC-MS/MS	splash10-001i-0910000000-b3cb895f045d519f2bf3
MS/MS Spectrum - Quattro_QQQ 40V, Positive	LC-MS/MS	splash10-00kb-5597500000-8495062a84b32e776f33
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-1920000000-07b98b36c7ef5d9ad048
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-0900000000-1ae1143763892a7aac22
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-001i-0900000000-460d58a5bb6a5eb5f55b
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0159-0900000000-34dc5c06413efae437da
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-8a5f15b863b7129c1288
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-072ffba5139b7324d27a
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00lr-0900000000-fdf3fc57eff19bfe8fd8
1H NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Taxonomy

Description: This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom: Organic compounds
Super Class: Benzenoids
Class: Benzene and substituted derivatives
Sub Class: Benzylethers
Direct Parent: Benzylethers
Alternative Parents: Pyridines and derivatives / Heteroaromatic compounds / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents: Benzylether / Pyridine / Heteroaromatic compound / Tertiary amine / Tertiary aliphatic amine / Azacycle / Organoheterocyclic compound / Ether / Dialkyl ether / Amine
Molecular Framework: Aromatic heteromonocyclic compounds
External Descriptors: tertiary amine, pyridines (CHEBI:51380)

Targets

Details1. Histamine H1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Histamine receptor activity
Specific Function: In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name: HRH1
Uniprot ID: P35367
Uniprot Name: Histamine H1 receptor
Molecular Weight: 55783.61 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Muscarinic acetylcholine receptor M1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Phosphatidylinositol phospholipase c activity
Specific Function: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name: CHRM1
Uniprot ID: P11229
Uniprot Name: Muscarinic acetylcholine receptor M1
Molecular Weight: 51420.375 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]

Details3. Nuclear receptor subfamily 1 group I member 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Curator comments: Antagonist at the canonical form of the receptor. Agonist at isoform 3 of the receptor.

General Function: Zinc ion binding
Specific Function: Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name: NR1I3
Uniprot ID: Q14994
Uniprot Name: Nuclear receptor subfamily 1 group I member 3
Molecular Weight: 39942.145 Da

References

Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]

Enzymes

Details1. CYP2B protein

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inducer
Curator comments: Doxylamine was found to induce CYP2B enzymes in mice; correlation with human subjects has not been established.

General Function: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function: Not Available
Gene Name: CYP2B
Uniprot ID: Q14097
Uniprot Name: CYP2B protein
Molecular Weight: 43147.81 Da

References

Bookstaff RC, Murphy VA, Skare JA, Minnema D, Sanzgiri U, Parkinson A: Effects of doxylamine succinate on thyroid hormone balance and enzyme induction in mice. Toxicol Appl Pharmacol. 1996 Dec;141(2):584-94. [PubMed:8975784]

Drug created on June 13, 2005 07:24 / Updated on January 21, 2020 16:12

Doxylamine

Identification

Structure for Doxylamine (DB00366)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

Enzymes

References