Identification

Name
Doxylamine
Accession Number
DB00366  (APRD00937)
Type
Small Molecule
Groups
Approved, Vet approved
Description

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. [PubChem]

Structure
Thumb
Synonyms
  • 2-(alpha-(2-(Dimethylamino)ethoxy)-alpha-methylbenzyl)pyridine
  • 2-Dimethylaminoethoxyphenylmethyl-2-picoline
  • Dossilamina
  • Doxilamina
  • Doxilminio
  • Doxylaminum
  • N,N-Dimethyl-2-(1-phenyl-1-(2-pyridinyl)ethoxy)ethanamine
  • Phenyl-2-pyridylmethyl-beta-N,N-dimethylaminoethyl ether
Product Ingredients
IngredientUNIICASInChI Key
Doxylamine succinateV9BI9B5YI2562-10-7KBAUFVUYFNWQFM-UHFFFAOYSA-N
Product Images
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
7 Select Sleep AidTablet25 mg/1Oral7 Eleven2014-08-05Not applicableUs
Aldex ANTablet, chewable5 mg/1OralPernix Therapeutics2010-01-202012-10-31Us
Basic Care Sleep AidTablet25 mg/1OralL. Perrigo Company2018-03-06Not applicableUs
Berkley and Jensen Sleep AidTablet25 mg/1OralBJWC2018-08-06Not applicableUs
Care One Sleep AidTablet25 mg/1OralAmerican Sales Company2004-06-292018-12-01Us
CareOne Nighttime Sleep AidTablet25 mg/1OralAmerican Sales Company2016-05-06Not applicableUs
Equaline Sleep AidTablet25 mg/1OralSupervalu2004-08-102015-11-01Us
Equate sleep aidTablet25 mg/1OralWalmart Stores1997-02-252014-01-27Us
Good Neighbor Pharmacy Sleep AidTablet25 mg/1OralAmerisource Bergen1997-06-26Not applicableUs
Good sense sleep aidTablet25 mg/1OralL. Perrigo Company1997-04-14Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
7 Select Night Time ReliefDoxylamine succinate (12.5 mg/30mL) + Acetaminophen (650 mg/30mL) + Dextromethorphan hydrobromide monohydrate (30 mg/30mL)SolutionOral7 Eleven2014-08-05Not applicableUs
7 Select Night Time ReliefDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)Capsule, liquid filledOral7 Eleven2014-04-17Not applicableUs
Acetaminophen Dextromethorphan HBr Doxylamine succinate Phenylephrine HClDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)Capsule, liquid filledOralCvs Pharmacy,inc2017-07-07Not applicableUs
Acetaminophen Dextromethorphan HBr Doxylamine succinate Phenylephrine HClDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)Capsule, liquid filledOralCVS Health2017-11-30Not applicableUs
ACETAMINOPHEN DEXTROMETHORPHAN HYDROBROMIDE and DOXYLAMINE SUCCINATEDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)Capsule, liquid filledOralJ.P. BUSINESS ENTERPRISE2014-12-01Not applicableUs
Acetaminophen Dextromethorphan Hydrobromide Doxylamine Succinate Phenylephrine hydrochlorideDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)Capsule, liquid filledOralHealthlife of Usa2017-07-072017-07-07Us
Acetaminophen Dextromethorphan Hydrobromide Doxylamine Succinate Phenylephrine HydrochlorideDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1) + Phenylephrine hydrochloride (5 mg/1)Capsule, liquid filledOralGranules India Limited2017-07-07Not applicableUs
ACETAMINOPHEN, DEXTROMETHORPHAN HYDROBROMIDE, and DOXYLAMINE SUCCINATEDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1)Capsule, liquid filledOralSpirit Pharmaceuticals, Llc2009-10-15Not applicableUs
Acetaminophen,Dextromethorphan,DoxylamineDoxylamine succinate (6.25 mg/1) + Acetaminophen (325 mg/1) + Dextromethorphan hydrobromide monohydrate (10 mg/1)Capsule, liquid filledOralAgile Pharmachem2014-05-01Not applicableUs
Acetaminophen/pseudoephedrine/dextromethorphan/doxylamineDoxylamine succinate (6.25 mg) + Acetaminophen (325 mg) + Dextromethorphan hydrobromide (15 mg) + Pseudoephedrine hydrochloride (30 mg)CapsuleOralApotex CorporationNot applicableNot applicableCanada
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.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
UMuscarinic acetylcholine receptor M1
antagonist
Human
UNuclear receptor subfamily 1 group I member 3Not AvailableHuman
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
PathwayCategory
Doxylamine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when Doxylamine is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
1,10-PhenanthrolineThe therapeutic efficacy of Doxylamine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Doxylamine.
2,5-Dimethoxy-4-ethylthioamphetamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
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
ChEBI
51380
ChEMBL
CHEMBL1004
Therapeutic Targets Database
DAP000859
PharmGKB
PA449419
Drugs.com
Drugs.com Drug Page
Wikipedia
Doxylamine
ATC Codes
R06AA59 — Doxylamine, combinationsR06AA09 — Doxylamine
AHFS Codes
  • 04:04.04 — Ethanolamine Derivatives
MSDS
Download (74 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableAllergic Rhinitis (AR) / Upper Respiratory Infections1
2Not Yet RecruitingTreatmentDiffuse Sclerosis Systemic / Interstitial Lung Disease (ILD) / Pulmonary Hypertension (PH) / Sclerosis, Progressive Systemic1
3CompletedPreventionHyperemesis Gravidarum / Pregnancy1
3CompletedTreatmentNausea and Vomiting of Pregnancy1
3Not Yet RecruitingTreatmentAcute Pyelonephritis / Complicated Urinary Tract Infections1
4RecruitingTreatmentMorning Sickness1
4RecruitingTreatmentSepsis1
Not AvailableRecruitingNot AvailableChildren;Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Amend
  • Centurion Labs
  • Chattem Chemicals Inc.
  • Deltex Pharmaceuticals Inc.
  • Duchesnay Inc.
  • Perrigo Co.
Dosage forms
FormRouteStrength
Tablet, chewableOral5 mg/1
Tablet, effervescentOral
Tablet, extended releaseOral
Capsule; kitOral
Kit
Kit97.5 mg/1
KitOral
Tablet, delayed releaseOral
TabletOral
Capsule, liquid filledOral
SyrupOral
Capsule, gelatin coatedOral
CapsuleOral
SolutionOral
TabletOral25 mg/1
Tablet, coatedOral
SyrupOral9.75 mg/5mL
Tablet, film coatedOral
Kit; tabletOral
Powder, for solutionOral
TabletOral25 mg
SolutionOral12.5 mg/1
LiquidOral
Prices
Unit descriptionCostUnit
Doxylamine succinate powder1.5USD g
Unisom sleep aid tablet0.34USD tablet
Sleep aid 25 mg tablet0.15USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6340695No2001-06-212021-06-21Us
US7560122No1999-01-252019-01-25Us
US9526703No2013-02-182033-02-18Us
US9375404No2013-02-182033-02-18Us
US9089489No2013-02-182033-02-18Us
US9937132No2013-02-182033-02-18Us

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)139 °C at 5.00E-01 mm HgPhysProp
water solubility1 g/ml (succinate salt)Not Available
logP2.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.541 mg/mLALOGPS
logP2.9ALOGPS
logP2.96ChemAxon
logS-2.7ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area25.36 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity82.24 m3·mol-1ChemAxon
Polarizability31.09 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9505
Blood Brain Barrier+0.9491
Caco-2 permeable+0.746
P-glycoprotein substrateSubstrate0.7449
P-glycoprotein inhibitor INon-inhibitor0.5123
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterInhibitor0.7507
CYP450 2C9 substrateNon-substrate0.8153
CYP450 2D6 substrateNon-substrate0.5432
CYP450 3A4 substrateSubstrate0.6801
CYP450 1A2 substrateNon-inhibitor0.9092
CYP450 2C9 inhibitorNon-inhibitor0.8957
CYP450 2D6 inhibitorInhibitor0.8361
CYP450 2C19 inhibitorNon-inhibitor0.8764
CYP450 3A4 inhibitorNon-inhibitor0.6894
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.736
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9183
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9218 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8765
hERG inhibition (predictor II)Inhibitor0.5398
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0ab9-9200000000-5a71de62862f9881c2a1
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-0040-0956300000-af11cf85a674e7db3735
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-001i-0910000000-b3cb895f045d519f2bf3
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-00kb-5597500000-8495062a84b32e776f33
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-1920000000-07b98b36c7ef5d9ad048
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-1ae1143763892a7aac22
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-460d58a5bb6a5eb5f55b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-0900000000-34dc5c06413efae437da
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-8a5f15b863b7129c1288
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-072ffba5139b7324d27a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-0900000000-fdf3fc57eff19bfe8fd8
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot 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

Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
Kind
Protein
Organism
Human
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
  1. 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

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
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
  1. 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 September 24, 2018 02:40