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IdentificationPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomyDoxylamine
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.
- Structure
Structure for Doxylamine (DB00366)
- 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 7 Select Sleep Aid Tablet 25 mg/1 Oral 7-Eleven 2014-08-05 Not applicable US 
Aldex AN Tablet, chewable 5 mg/1 Oral Pernix Therapeutics 2010-01-20 2012-10-31 US Basic Care Sleep Aid Tablet 25 mg/1 Oral L. Perrigo Company 2018-03-06 Not applicable US Berkley and Jensen Sleep Aid Tablet 25 mg/1 Oral BJWC 2018-08-06 Not applicable US Care One Sleep Aid Tablet 25 mg/1 Oral American Sales Company 2004-06-29 2018-12-01 US CareOne Nighttime Sleep Aid Tablet 25 mg/1 Oral American Sales Company 2016-05-06 Not applicable US Equaline Sleep Aid Tablet 25 mg/1 Oral Supervalu 2004-08-10 2015-11-01 US Equate sleep aid Tablet 25 mg/1 Oral Walmart Stores 1997-02-25 2014-01-27 US Good Neighbor Pharmacy Sleep Aid Tablet 25 mg/1 Oral Amerisource Bergen 1997-06-26 Not applicable US Good sense sleep aid Tablet 25 mg/1 Oral L. Perrigo Company 1997-04-14 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End 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 Not applicable US 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 Not applicable US 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 US 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 US 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 US 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 US 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 US 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 US 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 US 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 Canada 
- Categories
- Agents producing tachycardia
- Aminoalkyl Ethers
- Anticholinergic Agents
- Antiemetics
- Antihistamines for Systemic Use
- Autonomic Agents
- Central Nervous System Agents
- Central Nervous System Depressants
- Ethanolamine Derivatives
- Gastrointestinal Agents
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine Receptor Antagonists
- Muscarinic Antagonists
- Neurotransmitter Agents
- Peripheral Nervous System Agents
- Potential QTc-Prolonging Agents
- Pyridines
- QTc Prolonging Agents
- 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
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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 antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UNuclear receptor subfamily 1 group I member 3 Not Available Humans - 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
Drug Interaction 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. - 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
- R06AA09 — Doxylamine
- R06AA — Aminoalkyl ethers
- R06A — ANTIHISTAMINES FOR SYSTEMIC USE
- R06 — ANTIHISTAMINES FOR SYSTEMIC USE
- R — RESPIRATORY SYSTEM
- 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 Infections 1 1 Not Yet Recruiting Treatment Bioavailability 1 2 Recruiting Treatment Diffuse Sclerosis Systemic / Interstitial Lung Disease (ILD) / Pulmonary Hypertension (PH) / Sclerosis, Progressive Systemic 1 3 Completed Prevention Hyperemesis Gravidarum / Pregnancy 1 3 Completed Treatment Nausea and Vomiting of Pregnancy 1 3 Not Yet Recruiting Treatment Acute Pyelonephritis / Complicated Urinary Tract Infections 1 4 Recruiting Treatment Morning Sickness 1 4 Recruiting Treatment Sepsis 1 Not Available Recruiting Not Available Children；Infection 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 Tablet, extended release Oral Capsule; kit Oral Kit Kit Oral Kit 97.5 mg/1 Tablet, delayed release Oral Tablet Oral Capsule, liquid filled Oral Syrup Oral Capsule Oral Solution Oral Tablet, coated Oral Syrup Oral 9.75 mg/5mL Tablet, film coated Oral Capsule, gelatin coated Oral Kit; tablet Oral Tablet Oral 25 mg/1 Powder, for solution Oral Tablet Oral 25 mg Liquid 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) US6340695 No 2002-01-22 2021-06-21 US US7560122 No 2009-07-14 2019-01-25 US US9526703 No 2016-12-27 2033-02-18 US US9375404 No 2016-06-28 2033-02-18 US US9089489 No 2015-07-28 2033-02-18 US US9937132 No 2018-04-10 2033-02-18 US
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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
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
- 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]
- 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]
- 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
- Kind
- Protein
- Organism
- Humans
- 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
- 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 April 23, 2019 16:43