T3DB: Doxylamine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2014-08-30 21:03:25 UTC

Update Date

2014-12-24 20:26:52 UTC

Accession Number

T3D4551

Identification

Common Name

Doxylamine

Class

Small Molecule

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]

Compound Type

Amine
Antiemetic
Drug
Ether
Food Toxin
Histamine H1 Antagonist
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
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

Chemical Formula

C₁₇H₂₂N₂O

Average Molecular Mass

270.369 g/mol

Monoisotopic Mass

270.173 g/mol

CAS Registry Number

469-21-6

IUPAC Name

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

Traditional Name

doxylamine

SMILES

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

InChI Identifier

InChI=1/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

InChI Key

InChIKey=HCFDWZZGGLSKEP-UHFFFAOYNA-N

Chemical Taxonomy

Description

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

Substituents

Benzylether
Pyridine
Heteroaromatic compound
Tertiary amine
Tertiary aliphatic amine
Azacycle
Organoheterocyclic compound
Ether
Dialkyl ether
Amine
Organic oxygen compound
Organooxygen compound
Organonitrogen compound
Organic nitrogen compound
Organopnictogen compound
Hydrocarbon derivative
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

tertiary amine (CHEBI:51380 )
pyridines (CHEBI:51380 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Liquid

Appearance

Not Available

Experimental Properties

Property	Value
Melting Point	< 25 °C
Boiling Point	139 °C at 5.00E-01 mm Hg
Solubility	1 g/ml (succinate salt)
LogP	2.5

Predicted Properties

Property	Value	Source
Water Solubility	0.54 g/L	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	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a59-7900000000-24e4f3f90dbbb5862928	2017-08-28	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-0040-0956300000-af11cf85a674e7db3735	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-001i-0910000000-b3cb895f045d519f2bf3	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-00kb-5597500000-8495062a84b32e776f33	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0292-0940000000-f369442eba5344b3ecb4	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-001i-1920000000-07b98b36c7ef5d9ad048	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-001i-0900000000-1ae1143763892a7aac22	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-001i-0900000000-460d58a5bb6a5eb5f55b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0159-0900000000-34dc5c06413efae437da	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-014i-0900000000-8a5f15b863b7129c1288	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-014i-0900000000-072ffba5139b7324d27a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-00lr-0900000000-fdf3fc57eff19bfe8fd8	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-001i-0900000000-4bd3999ccd0a2246f1bf	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-001i-1920000000-1fbd7581ebf1730dac6d	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0159-1900000000-37f4e915e528d2466b80	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-001i-0900000000-a056c64c9344a9559905	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0159-0900000000-0ab3cbbe5a34cba77313	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-014i-0900000000-1a3a34606ccd3aa3009c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-014i-0900000000-07c546b389aa80244f62	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-1190000000-e7b1a3b0a0368fc310df	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00e9-5790000000-7402b4fd77afe325c64b	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00di-9510000000-b9439d5014a66b7857ec	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-014i-1290000000-1725573962a3041ca617	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-014j-1690000000-44de19831bffecc1c412	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-009t-5900000000-caa39da176327be2a9c2	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00kb-0960000000-a2cc3fcbeb38ca35de58	2021-09-22	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0ab9-9200000000-5a71de62862f9881c2a1	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, H₂O, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Readily absorbed via the gastrointestinal tract.

Mechanism of Toxicity

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

Metabolism

Hepatic. Half Life: 10 hours

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

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

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB00366

HMDB ID

Not Available

PubChem Compound ID

3162

ChEMBL ID

CHEMBL1004

ChemSpider ID

3050

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

51380

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Doxylamine

References

Synthesis Reference

Not Available

MSDS

T3D4551.pdf

General References

Not Available

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Histamine H1 receptor

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 catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:: HRH1
Uniprot ID:: P35367
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. [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. [17016423 ]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Target Details

2. Muscarinic acetylcholine receptor M1

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 action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM1
Uniprot ID:: P11229
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. [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. [17016423 ]

Target Details

3. Nuclear receptor subfamily 1 group I member 3

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 responsive element module of the human CYP2B6 gene and the CYP3A4 xenobiotic response element.
Gene Name:: NR1I3
Uniprot ID:: Q14994
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. [20869355 ]

Doxylamine (T3D4551)

Structure for T3D4551: Doxylamine

Targets

References

References

References