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Identification
NameDoxylamine
Accession NumberDB00366  (APRD00937)
TypeSmall Molecule
GroupsApproved
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
SynonymLanguageCode
2-(alpha-(2-(Dimethylamino)ethoxy)-alpha-methylbenzyl)pyridineNot AvailableNot Available
2-Dimethylaminoethoxyphenylmethyl-2-picolineNot AvailableNot Available
DossilaminaNot AvailableDCIT
DoxilaminaNot AvailableNot Available
DoxilminioSpanishINN
DoxylaminumLatinINN
N,N-Dimethyl-2-(1-phenyl-1-(2-pyridinyl)ethoxy)ethanamineNot AvailableNot Available
Phenyl-2-pyridylmethyl-beta-N,N-dimethylaminoethyl etherNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixtures
Brand NameIngredients
DiclectinDoxylamine Succinate + Pyridoxine Hydrochloride
DICLEGISPyridoxine + Doxylamine
Extra Strength Tylenol Sinus Nighttime CapletAcetaminophen + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Mercodol with DecaprynDoxylamine Succinate + Etafedrin Hydrochloride + Hydrocodone Bitartrate + Sodium Citrate
Neocitran Cold & Flu SyrupAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Night Relief Cold and Flu Liquid CapsulesAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Nighttime Cold and Flu Liquid CapsulesAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Nighttime Cold and Flu ReliefAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Nighttime Liquid Capsules Cold/Flu MedicineAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Nitetime Cold MedicineAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Nyquil LiquicapsAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Regular Strength Sinus MedicationAcetaminophen + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Sinus MedicationAcetaminophen + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Sinus Medication Night TabletsAcetaminophen + Doxylamine Succinate + Pseudoephedrine Hydrochloride
Tylenol Cold & Flu NighttimeAcetaminophen + Dextromethorphan Hydrobromide + Doxylamine Succinate + Pseudoephedrine Hydrochloride
SaltsNot Available
Categories
CAS number469-21-6
WeightAverage: 270.3694
Monoisotopic: 270.173213336
Chemical FormulaC17H22N2O
InChI KeyHCFDWZZGGLSKEP-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
Taxonomy
DescriptionThis 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).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • Pyridine
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed 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.
PharmacodynamicsDoxylamine 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 actionLike other antihistamines, doxylamine acts by competitively inhibiting histamine at H1 receptors. It also has substantial sedative and anticholinergic effects.
AbsorptionReadily absorbed via the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life10 hours
ClearanceNot Available
ToxicitySigns 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateNon-inhibitor0.8957
CYP450 2D6 substrateInhibitor0.8361
CYP450 2C19 substrateNon-inhibitor0.8764
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage formsNot Available
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.
PatentsNot Available
Properties
StateLiquid
Experimental Properties
PropertyValueSource
melting point< 25 °CPhysProp
boiling point139 °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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS/MSMS1D NMR2D NMR
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesR06AA09
AHFS Codes
  • 04:04.04
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74 KB)
Interactions
Drug Interactions
Drug
DonepezilPossible antagonism of action
GalantaminePossible antagonism of action
PramlintideMay cause additive slowing of GI motility.
TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxylamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
TrimethobenzamideTrimethobenzamide and Doxylamine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
TriprolidineTriprolidine and Doxylamine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
TrospiumTrospium and Doxylamine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Food InteractionsNot Available

Targets

1. Histamine H1 receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Histamine H1 receptor P35367 Details

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
  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
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Muscarinic acetylcholine receptor M1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M1 P11229 Details

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
  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

Enzymes

1. CYP2B protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
CYP2B protein Q14097 Details

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

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10