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Details

Stereochemistry ABSOLUTE
Molecular Formula C76H52O46.C17H21NO
Molecular Weight 1956.5532
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENHYDRAMINE TANNATE

SMILES

CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2.OC3=CC(=CC(O)=C3O)C(=O)OC4=C(O)C(O)=CC(=C4)C(=O)OC[C@H]5O[C@@H](OC(=O)C6=CC(OC(=O)C7=CC(O)=C(O)C(O)=C7)=C(O)C(O)=C6)[C@H](OC(=O)C8=CC(OC(=O)C9=CC(O)=C(O)C(O)=C9)=C(O)C(O)=C8)[C@@H](OC(=O)C%10=CC(OC(=O)C%11=CC(O)=C(O)C(O)=C%11)=C(O)C(O)=C%10)[C@@H]5OC(=O)C%12=CC(OC(=O)C%13=CC(O)=C(O)C(O)=C%13)=C(O)C(O)=C%12

InChI

InChIKey=JUPRSNHHBNEGEK-HBNMXAOGSA-N
InChI=1S/C76H52O46.C17H21NO/c77-32-1-22(2-33(78)53(32)92)67(103)113-47-16-27(11-42(87)58(47)97)66(102)112-21-52-63(119-72(108)28-12-43(88)59(98)48(17-28)114-68(104)23-3-34(79)54(93)35(80)4-23)64(120-73(109)29-13-44(89)60(99)49(18-29)115-69(105)24-5-36(81)55(94)37(82)6-24)65(121-74(110)30-14-45(90)61(100)50(19-30)116-70(106)25-7-38(83)56(95)39(84)8-25)76(118-52)122-75(111)31-15-46(91)62(101)51(20-31)117-71(107)26-9-40(85)57(96)41(86)10-26;1-18(2)13-14-19-17(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h1-20,52,63-65,76-101H,21H2;3-12,17H,13-14H2,1-2H3/t52-,63-,64+,65-,76+;/m1./s1

HIDE SMILES / InChI
Molecular Formula C76H52O46
Molecular Weight 1701.1985
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 3
Optical Activity UNSPECIFIED
Molecular Formula C17H21NO
Molecular Weight 255.3547
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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.

CNS Activity

Originator

Rieveschl, G.
13
Curator's Comment: Diphenhydramine was discovered by George Rieveschl, in 1943 at the University of Cincinnati

Approval Year

1946
58
Targets

Targets

Primary TargetPharmacologyConditionPotency
Histamine H1 receptor
316
Target ID: P35367
Gene ID: 3269.0
Gene Symbol: HRH1
Target Organism: Homo sapiens (Human)
Antagonist
2849
Antagonist
2849
 7.9 null [pKi]
Antagonist
2849
Blocker
555
 2.7 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8583
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

2014
Palliative
Approved
8583
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
93 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28967696
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
887 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
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
667 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.5 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
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
9.2 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/3760245
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
18.3%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/2369804
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:
https://pubmed.ncbi.nlm.nih.gov/22158278/
unknown, 13 months
Health Status: unknown
Age Group: 13 months
Sex: F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
Other AEs: QT interval prolonged...
Other AEs:
QT interval prolonged (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Disc. AE: Liver injury, Vomiting...
AEs leading to
discontinuation/dose reduction:
Liver injury (1 patient)
Vomiting (1 patient)
Jaundice (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
Other AEs: Hypertension...
Other AEs:
Hypertension (below serious, 5 patients)
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
AEs

AEs

AESignificanceDosePopulation
QT interval prolonged 1 patient
600 mg single, oral
Overdose
Dose: 600 mg
Route: oral
Route: single
Dose: 600 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
unknown, 13 months
Health Status: unknown
Age Group: 13 months
Sex: F
Sources:
https://pubmed.ncbi.nlm.nih.gov/22158278/
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:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
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:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
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:
https://pubmed.ncbi.nlm.nih.gov/28246565
unhealthy, 28 years
Health Status: unhealthy
Age Group: 28 years
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/28246565
Hypertension below serious, 5 patients
50 mg single, intravenous
Dose: 50 mg
Route: intravenous
Route: single
Dose: 50 mg
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
unhealthy
Health Status: unhealthy
Sources:
https://clinicaltrials.gov/ct2/show/NCT01967433
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1946
substrate
1193
substrate
1388

inhibitor
2507

OverviewOther

Other InhibitorOther SubstrateOther Inducer
OCT1
620

OCT2
779

OCT3
159

MATE1
415

MATE2
267
CYP1A1
389

CYP1A2
1197

CYP2A6
626

CYP2B6
776

CYP2C8
810

CYP2C18
149

CYP2C19
1119

CYP2E1
729

CYP3A5
446

CYP4A11
137

UGT1A3
470

UGT1A4
399

UGT2B10
131
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
2546
 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
OCT2
782
 yes [IC50 15 uM]
OCT1
656
 yes [IC50 3.4 uM]
OCT3
161
 yes [IC50 695 uM]
MATE2
267
 yes [Ki 266.5 uM]
MATE1
416
 yes [Ki 87 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1388
 major
UGT2B10
131
 major
CYP1A2
1197
 minor
CYP2C19
1119
 minor
UGT1A3
470
 minor
UGT1A4
399
 minor
CYP2A6
626
 no
CYP2E1
729
 no
CYP4A11
137
 no
CYP1A1
389
 weak
CYP2B6
776
 weak
CYP2C18
149
 weak
CYP2C8
810
 weak
CYP2C9
1193
 weak
CYP3A4
1946
 weak
CYP3A5
446
 weak
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4636
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4636
ChemicalBook
CB6196202
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6196202
eMolecules
716786
https://www.emolecules.com/cgi-bin/more?vid=716786
MolPort
MolPort-001-783-508
https://www.molport.com/shop/molecule-link/MolPort-001-783-508
ZINC
ZINC000000020244
http://zinc15.docking.org/substances/ZINC000000020244
PubMed

PubMed

TitleDatePubMed
Evaluation of diphenhydramine in talc induced type 2 diabetes mellitus in Wistar rats.
2018-01
A patient with anaphylaxis to diphenhydramine without cross-reactivity to loratadine.
2017-09-12
Diphenhydramine: pharmacokinetics and pharmacodynamics in elderly adults, young adults, and children.
1990-07
Diphenhydramine.
1986-02
Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines).
1985-11-01
Patents

Patents

US9592197
10

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
Curator's Comment: In vitro, [14C] diphenhydramine was accumulated by a saturable, energy-requiring system in choroid plexus. The results show that diphenhydramine, unlike diazepam, is transported between blood, brain and cerebrospinal fluid, in part, by saturable, carrier-mediated transport processes at both the blood-brain and blood-cerebrospinal fluid barriers.
Unknown
Substance Class Chemical
Created
by admin
on Mon Mar 31 20:21:47 GMT 2025
Edited
by admin
on Mon Mar 31 20:21:47 GMT 2025
Record UNII
OPI52249ZG
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DIPHENHYDRAMINE TANNATE
WHO-DD  
Common Name English
2-(DIPHENYLMETHOXY)-N,N-DIMETHYLETHYLAMINE TANNATE
Preferred Name English
DIPHENHYDRAMINE TANNATE [WHO-DD]
Common Name English
DIPHENHYDRAMINE TANNATE [JAN]
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL657
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
FDA UNII
OPI52249ZG
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
PUBCHEM
165411844
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
RXCUI
360283
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY RxNorm
SMS_ID
100000087518
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
SMS_ID
100000087518
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
EVMPD
SUB01775MIG
Created by admin on Mon Mar 31 20:21:47 GMT 2025 , Edited by admin on Mon Mar 31 20:21:47 GMT 2025
PRIMARY
Related Record Type Details
Structure of DIPHENHYDRAMINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of DIPHENHYDRAMINE
ACTIVE MOIETY
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