Identification

Name
Bromodiphenhydramine
Accession Number
DB01237  (APRD00710)
Type
Small Molecule
Groups
Approved
Description

Bromodiphenhydramine is an ethanolamine antihistamine with antimicrobial property. Bromodiphenhydramine is used in the control of cutaneous allergies. Ethanolamine antihistamines produce marked sedation in most patients.

Structure
Thumb
Synonyms
  • 2-(p-bromo-α-phenylbenzyloxy)-N,N-dimethylethylamine
  • Bromazina
  • Bromazine
  • Bromazinum
  • β-(p-bromobenzhydryloxy)ethyldimethylamine
  • β-dimethylaminoethyl p-bromobenzhydryl ether
Product Ingredients
IngredientUNIICASInChI Key
Bromodiphenhydramine hydrochloride202J683U971808-12-4ZQDJSWUEGOYDGT-UHFFFAOYSA-N
Categories
UNII
T032BI7727
CAS number
118-23-0
Weight
Average: 334.251
Monoisotopic: 333.072826914
Chemical Formula
C17H20BrNO
InChI Key
NUNIWXHYABYXKF-UHFFFAOYSA-N
InChI
InChI=1S/C17H20BrNO/c1-19(2)12-13-20-17(14-6-4-3-5-7-14)15-8-10-16(18)11-9-15/h3-11,17H,12-13H2,1-2H3
IUPAC Name
{2-[(4-bromophenyl)(phenyl)methoxy]ethyl}dimethylamine
SMILES
CN(C)CCOC(C1=CC=CC=C1)C1=CC=C(Br)C=C1

Pharmacology

Indication

For management of symptoms related to hay fever and other types of allergy and used to help bring up phlegm, thin secretions, and make a cough productive.

Pharmacodynamics

Bromodiphenhydramine is an antihistamine of the ethanolamine class. Ethanolamine antihistamines have significant antimuscarinic activity and produce marked sedation in most patients. In addition to the usual allergic symptoms, the drug also treats irritant cough and nausea, vomiting, and vertigo associated with motion sickness. It also is used commonly to treat drug-induced extrapyramidal symptoms as well as to treat mild cases of Parkinson's disease. Rather than preventing the release of histamine, as do cromolyn and nedocromil, Bromodiphenhydramine competes with free histamine for binding at HA-receptor sites. Bromodiphenhydramine competitively antagonizes the effects of histamine on HA-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Ethanolamine derivatives have greater anticholinergic activity than do other antihistamines, which probably accounts for the antidyskinetic action of Bromodiphenhydramine. This anticholinergic action appears to be due to a central antimuscarinic effect, which also may be responsible for its antiemetic effects, although the exact mechanism is unknown.

Mechanism of action

Bromodiphenhydramine competes with free histamine for binding at HA-receptor sites. This antagonizes the effects of histamine on HA-receptors, leading to a reduction of the negative symptoms brought on by histamine HA-receptor binding.

TargetActionsOrganism
AHistamine H1 receptor
antagonist
Human
Absorption

Well absorbed in the digestive tract.

Volume of distribution
Not Available
Protein binding

96%

Metabolism

Hepatic (cytochrome P-450 system); some renal.

Route of elimination
Not Available
Half life

1 to 4 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
Bromodiphenhydramine H1-Antihistamine ActionDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Bromodiphenhydramine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative activities of Bromodiphenhydramine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Bromodiphenhydramine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Bromodiphenhydramine.
AmphetamineAmphetamine may decrease the sedative and stimulatory activities of Bromodiphenhydramine.
BenzphetamineBenzphetamine may decrease the sedative and stimulatory activities of Bromodiphenhydramine.
Benzylpenicilloyl PolylysineBromodiphenhydramine may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Bromodiphenhydramine.
ChlorphentermineChlorphentermine may decrease the sedative activities of Bromodiphenhydramine.
DextroamphetamineDextroamphetamine may decrease the sedative activities of Bromodiphenhydramine.
Food Interactions
Not Available

References

Synthesis Reference
US2527963
General References
Not Available
External Links
Human Metabolome Database
HMDB0015367
PubChem Compound
2444
PubChem Substance
46506082
ChemSpider
2350
BindingDB
81465
ChEBI
59177
ChEMBL
CHEMBL1201245
Therapeutic Targets Database
DAP001072
PharmGKB
PA164760854
Wikipedia
Bromodiphenhydramine
ATC Codes
R06AA01 — Bromazine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00345 mg/mLALOGPS
logP4.16ALOGPS
logP4.42ChemAxon
logS-5ALOGPS
pKa (Strongest Basic)8.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.55 m3·mol-1ChemAxon
Polarizability33.48 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9871
Blood Brain Barrier+0.9525
Caco-2 permeable+0.7916
P-glycoprotein substrateSubstrate0.6199
P-glycoprotein inhibitor INon-inhibitor0.6681
P-glycoprotein inhibitor IINon-inhibitor0.7076
Renal organic cation transporterInhibitor0.7733
CYP450 2C9 substrateNon-substrate0.8289
CYP450 2D6 substrateSubstrate0.7231
CYP450 3A4 substrateSubstrate0.6411
CYP450 1A2 substrateInhibitor0.7747
CYP450 2C9 inhibitorNon-inhibitor0.8483
CYP450 2D6 inhibitorInhibitor0.8438
CYP450 2C19 inhibitorNon-inhibitor0.719
CYP450 3A4 inhibitorNon-inhibitor0.917
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5526
Ames testNon AMES toxic0.8547
CarcinogenicityNon-carcinogens0.6627
BiodegradationNot ready biodegradable0.9892
Rat acute toxicity2.7517 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5627
hERG inhibition (predictor II)Inhibitor0.7917
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
GC-MS Spectrum - EI-BGC-MSsplash10-0a4i-9000000000-53342d9a3abac3e5c130
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Benzylethers / Bromobenzenes / Aryl bromides / Trialkylamines / Dialkyl ethers / Organopnictogen compounds / Organobromides / Hydrocarbon derivatives
Substituents
Diphenylmethane / Benzylether / Bromobenzene / Halobenzene / Aryl bromide / Aryl halide / Tertiary aliphatic amine / Tertiary amine / Ether / Dialkyl ether
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
organobromine compound, tertiary amino compound (CHEBI:59177)

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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Ullrich KJ, Rumrich G, David C, Fritzsch G: Bisubstrates: substances that interact with renal contraluminal organic anion and organic cation transport systems. I. Amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines. Pflugers Arch. 1993 Nov;425(3-4):280-99. [PubMed:8309790]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Ullrich KJ, Rumrich G, David C, Fritzsch G: Bisubstrates: substances that interact with renal contraluminal organic anion and organic cation transport systems. I. Amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines. Pflugers Arch. 1993 Nov;425(3-4):280-99. [PubMed:8309790]

Drug created on June 13, 2005 07:24 / Updated on September 13, 2018 16:05