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Details

Stereochemistry ACHIRAL
Molecular Formula C17H21NO
Molecular Weight 255.3554
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENHYDRAMINE

SMILES

CN(C)CCOC(c1ccccc1)c2ccccc2

InChI

InChIKey=ZZVUWRFHKOJYTH-UHFFFAOYSA-N
InChI=1S/C17H21NO/c1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,17H,13-14H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C17H21NO
Molecular Weight 255.3554
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Diphenhydramine is an antihistamine which is used in the combination with naproxen sodium for the relief of occasional sleeplessness when associated with minor aches and pains. Diphenhydramine has a role nighttime sleep-aid and naproxen sodium is a pain reliever. In addition, diphenhydramine used in relieving symptoms in patients with moderate-to-severe seasonal allergic rhinitis. Diphenhydramine acts as an antagonist of histamine H1 receptor. Besides, was shown potential to repurpose diphenhydramine as an anti-melanoma therapeutic agent, it induces melanoma cell apoptosis by suppressing STAT3/MCL-1 survival signaling pathway.

Originator

Curator's Comment:: Diphenhydramine was discovered by George Rieveschl, in 1943 at the University of Cincinnati

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P35367
Gene ID: 3269
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
7.90000000000000036 null [pKi]
2.70000000000000018 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
ALEVE PM

Approved Use

for relief of occasional sleeplessness when associated with minor aches and pains; helps you fall asleep and stay asleep

Launch Date

1389830400000
Palliative
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
93 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: UNKNOWN
age: ADOLESCENT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
667 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
887 ng × h/mL
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
9.2 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.5 h
50 mg single, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18.3%
DIPHENHYDRAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
unknown, 13 months
Health Status: unknown
Age Group: 13 months
Sex: F
Sources:
Other AEs: QT interval prolonged...
Other AEs:
QT interval prolonged (1 patient)
Sources:
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
Disc. AE: Liver injury, Vomiting...
AEs leading to
discontinuation/dose reduction:
Liver injury (1 patient)
Vomiting (1 patient)
Jaundice (1 patient)
Sources:
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
unhealthy
Health Status: unhealthy
Sources:
Other AEs: Hypertension...
Other AEs:
Hypertension (below serious, 5 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
QT interval prolonged 1 patient
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
unknown, 13 months
Health Status: unknown
Age Group: 13 months
Sex: F
Sources:
Jaundice 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
Liver injury 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
Vomiting 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
Hypertension below serious, 5 patients
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
weak [IC50 11 uM]
yes (co-administration study)
Comment: diphenhydramine coadministration significantly altered the pharmacokinetics, heart rate, systolic blood pressure, and peak acceleration response of metoprolol in extensive metabolizers but not in poor metabolizers
yes [IC50 15 uM]
yes [IC50 3.4 uM]
yes [IC50 695 uM]
yes [Ki 266.5 uM]
yes [Ki 87 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
minor
minor
minor
minor
no
no
no
weak
weak
weak
weak
weak
weak
weak
PubMed

PubMed

TitleDatePubMed
Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines).
1985 Nov-Dec
Patents

Patents

Sample Use Guides

occasional sleeplessness: do not take more than directed; drink a full glass of water with each dose, adults and children 12 years and over: take 2 caplets at bedtime, do not take more than 2 caplets in 24 hours, if taken with food, this product may take longer to work
Route of Administration: Oral
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:21:06 UTC 2021
Edited
by admin
on Fri Jun 25 22:21:06 UTC 2021
Record UNII
8GTS82S83M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIPHENHYDRAMINE
HSDB   INN   MART.   MI   VANDF   WHO-DD  
INN  
Official Name English
ORPHENADRINE CITRATE SPECIFIED IMPURITY D [EP]
Common Name English
DIPHENHYDRAMINE [INN]
Common Name English
DIPHENHYDRAMINE [JAN]
Common Name English
ORPHENADRINE CITRATE IMPURITY D [EP]
Common Name English
DIPHENHYDRAMINE [MI]
Common Name English
2-(DIPHENYLMETHOXY)-N,N-DIMETHYLETHYLAMINE
Systematic Name English
DIPHENHYDRAMINE [WHO-DD]
Common Name English
RESTAMIN
Brand Name English
DIPHENHYDRAMINE [MART.]
Common Name English
ETHANAMINE, 2-(DIPHENYLMETHOXY)-N,N-DIMETHYL-
Systematic Name English
DIPHENHYDRAMINE [HSDB]
Common Name English
ORPHENADRINE IMPURITY D
Common Name English
DIPHENHYDRAMINE [VANDF]
Common Name English
DIPHENHDYRA [VANDF]
Common Name English
Classification Tree Code System Code
WHO-VATC QD04AA32
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
WHO-VATC QR06AA52
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
WHO-VATC QR06AA02
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
NDF-RT N0000175587
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
WHO-ATC R06AA02
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
WHO-ATC R06AA52
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
LIVERTOX 314
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
NDF-RT N0000000190
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
NCI_THESAURUS C267
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
NCI_THESAURUS C29578
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
WHO-ATC D04AA32
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
Code System Code Type Description
EVMPD
SUB07211MIG
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
DRUG CENTRAL
916
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
MERCK INDEX
M4609
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY Merck Index
INN
1774
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
IUPHAR
1224
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL657
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
LACTMED
Diphenhydramine
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
EPA CompTox
58-73-1
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
RXCUI
3498
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
200-396-7
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
PUBCHEM
3100
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
CAS
58-73-1
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
DRUG BANK
DB01075
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
WIKIPEDIA
DIPHENHYDRAMINE
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
MESH
D004155
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
NCI_THESAURUS
C61728
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
FDA UNII
8GTS82S83M
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
HSDB
3066
Created by admin on Fri Jun 25 22:21:07 UTC 2021 , Edited by admin on Fri Jun 25 22:21:07 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
POTENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
N-demethylation of diphenhydramine is mainly catalyzed by CYP2D6 as a high-affinity P450 isozyme at a clinically relevant concentration.
MAJOR
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
CYP1A2, CYP2C9, and CYP2C19 are involved in the metabolism of diphenhydramine as low-affinity P450 isozymes.
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
CYP1A2, CYP2C9, and CYP2C19 are involved in the metabolism of diphenhydramine as low-affinity P450 isozymes.
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
CYP1A2, CYP2C9, and CYP2C19 are involved in the metabolism of diphenhydramine as low-affinity P450 isozymes.
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
SUBSTANCE->BASIS OF STRENGTH
Related Record Type Details
METABOLITE -> PARENT
METABOLITE -> PARENT
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY