diphenhydramine

Trade name: benadryl

Small moleculeapproved

Approved

Mar 4, 1946

Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particularly at higher doses. This may manifest as agitation, anxiety, or restlessness rather than sedation. It is a first-generation H1-antihistamine and it works by blocking certain effects of histamine, which produces its antihistamine and sedative effects. Diphenhydramine is also a potent anticholinergic. It is mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremors in parkinsonism, and nausea. It is taken by mouth, injected into a vein, injected into a muscle, or applied to the skin. Maximal effect is typically around two hours after a dose, and effects can last for up to seven hours. — Wikipedia

Clinical trial activity

201 trials · 158 clinical orgs · 69 marketing orgs

Phase 1

Phase 2

102

Phase 3

Phase 4

Earliest trial started Nov 2, 1999 (NCT00000875)

Timeline

1940s

Mar 4, 1946
Earliest FDA Approval
Mar 4, 1946
McNeil — NDA Secondary Org

1950s

Jun 1, 1951
Parke-Davis — First NDA Organization
Jun 1, 1951
Parke-Davis — NDA Organization
Apr 28, 1954
Forest Laboratories — Marketing Organization
Apr 28, 1954
Forest Laboratories — NDA Secondary Org

1970s

May 31, 1972
Alta Pharma — Marketing Organization
Aug 7, 1972
American Home Products — Marketing Organization
Aug 24, 1972
Barr Laboratories — Marketing Organization
Aug 24, 1972
Heritage Pharma — Marketing Organization
Sep 27, 1972
Watson Pharmaceuticals — Marketing Organization
Nov 3, 1972
Fosun — Marketing Organization
Nov 27, 1972
West-Ward Pharmaceutical — Marketing Organization
Dec 20, 1972
Roxane Laboratories — Marketing Organization
Jan 12, 1973
MK Labs — Marketing Organization
Aug 13, 1973
Whiteworth Towne Paulsen — Marketing Organization
Oct 12, 1973
Eurohlth Intl Sarl — Marketing Organization
Oct 12, 1973
Nexgen Pharma, Inc — Marketing Organization
Oct 25, 1973
Hikma — Marketing Organization
Nov 14, 1973
Impax Laboratories — Marketing Organization
Jan 18, 1974
Bausch Health Companies — Marketing Organization
Jan 29, 1974
Dr. Reddy's Laboratories — Marketing Organization
Feb 13, 1974
Lannett Company, Inc. — Marketing Organization
Dec 19, 1974
Mutual Pharmaceutical — Marketing Organization
Mar 15, 1976
International Medication — Marketing Organization
Sep 22, 1977
Lumara Health — Marketing Organization
Jan 25, 1979
Belmar Pharmacy — Marketing Organization
Feb 8, 1979
Newtron Pharmaceuticals — Marketing Organization
Feb 26, 1979
Upsher-Smith Laboratories — Marketing Organization
Oct 30, 1979
Teva — Marketing Organization

1980s

Mar 31, 1981
Lyphomed, Inc. — Marketing Organization
Dec 7, 1981
Vanguard — Marketing Organization
Jan 25, 1982
Puracap Pharmaceutical — Marketing Organization
Feb 10, 1982
Pharmaceutical Associates — Marketing Organization
Mar 2, 1982
Lederle — Marketing Organization
Mar 2, 1982
American Cyanamid — Marketing Organization
Jan 27, 1983
LNK International — Marketing Organization
Oct 3, 1983
Halsey — Marketing Organization
Oct 12, 1984
Wockhardt — Marketing Organization
Jan 2, 1987
Sun Pharmaceuticals — Marketing Organization

1990s

Sep 28, 1990
Akorn, Inc. — Marketing Organization
Sep 28, 1990
Hi Tech Pharmaceuticals — Marketing Organization
Sep 18, 1991
Morton Grove Pharmaceuticals — Marketing Organization
Nov 20, 1998
Hospira — Marketing Organization
Jan 1, 1999
Earliest Phase 3 Sponsor(trial)

2000s

Jan 1, 2000
Earliest Phase 2 Sponsor(trial)
Jan 1, 2002
Earliest Phase 1 Sponsor(trial)
May 28, 2002
Abraxis — Marketing Organization
Jul 12, 2005
Mylan — Marketing Organization
Dec 21, 2005
Pfizer — Marketing Organization
Dec 21, 2005
GlaxoSmithKline — NDA Secondary Org

2010s

Nov 22, 2010
Bionpharma Inc — Marketing Organization
Mar 5, 2012
Strides Pharma Science — Marketing Organization
Mar 26, 2013
Fresenius — Marketing Organization
Jan 17, 2014
Bayer — Marketing Organization
Jan 17, 2014
Bayer — NDA Secondary Org
Aug 22, 2018
Micro Labs Ltd India — Marketing Organization
Oct 23, 2018
Amneal Pharmaceuticals — Marketing Organization
Jan 25, 2019
Actavis — Marketing Organization
Jan 25, 2019
P&L Development — Marketing Organization
Feb 14, 2019
Aurobindo Pharma — Marketing Organization
May 10, 2019
Perrigo — Marketing Organization
Aug 22, 2019
Apotex — Marketing Organization
Aug 22, 2019
Corepharma — Marketing Organization

2020s

Sep 24, 2020
Granules India — Marketing Organization

Indications

Studied for

Mechanism of action

Histamine H1 receptorANTAGONIST
HRH1 antagonist
- Histamine H1 receptor (HRH1) ↗

Combination products

advil pm
with ibuprofen
aleve pm
with naproxen
ambenyl
with codeine
benylin
with pseudoephedrine

Approval history

approvedMar 4, 1946

Chemistry & pharmacology

Loading structure…

SMILES

CC(CN1c2ccccc2Sc2ccccc21)N(C)C.Cl

Mol. weight: 320.89 g/mol
Lipinski Ro5: Pass
Rule of 3: No
Chirality: Racemic Mixture
Inorganic: No
Polymer: No
Delivery: Oral, Parenteral, Topical
Availability: Prescription Only

Oral

Yes

Parenteral

Yes

Topical

Yes

Black box warning

Sources

Also known as

2-(benzhydryloxy)-n,n-dimethylethylamine
2-(benzhydryloxy)-n,n-dimethylethylamine
2-diphenylmethoxy-n,n-demthylethanamine
2-diphenylmethoxy-n,n-demthylethanamine
2-(p-bromo-alpha-phenylbenzyloxy)-n,n-dimethylethylamine
2-(p-bromo-alpha-phenylbenzyloxy)-n,n-dimethylethylamine
alledryl
alledryl
alpha-(2-dimethylaminoethoxy)diphenylmethane
alpha-(2-dimethylaminoethoxy)diphenylmethane
ambodryl
ambodryl
ambodryl
amodryl
amodryl
antitussive
antitussive
beldin
beldin
belix
belix
benadryl
benadryl
benadryl
benadryl
benadryl
benadryl
benadryl
benadryl
benadryl preservative free
benadryl preservative free
benylin
benylin
benzhydramine
beta-dimethylaminoethanol diphenylmethyl ether
beta-dimethylaminoethanol diphenylmethyl ether
beta-dimethylaminoethyl benzhydryl ether
beta-dimethylaminoethyl benzhydryl ether
beta-dimethylaminoethyl p-bromobenzhydryl ether
beta-dimethylaminoethyl p-bromobenzhydryl ether
beta-(p-bromobenzhydryloxy)ethyldimethylamine
beta-(p-bromobenzhydryloxy)ethyldimethylamine
bietanautine
bromanautine
bromazina
bromazina
bromazine
bromazine
bromazine
bromazine
bromazine
bromazine
bromazine
bromazinum
bromazinum
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine
bromodiphenhydramine hcl
bromodiphenhydramine hcl
bromodiphenhydramine hcl
bromodiphenhydramine hydrochloride
bromodiphenhydramine hydrochloride
bromodiphenhydramine hydrochloride
bromodiphenhydramine hydrochloride
bromodiphenhydramine hydrochloride
caladryl
caladryl
coltex
dibenil
dibenil
difenhidramina
difenhidramina
dimedrol
dimedrol
diphen
diphen
diphenhdramine
diphenhydramien
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine
diphenhydramine citrate
diphenhydramine citrate
diphenhydramine citrate
diphenhydramine citrate
diphenhydramine hcl
diphenhydramine hcl
diphenhydramine hcl
diphenhydramine hcl
diphenhydramine hydrochloride
diphenhydramine hydrochloride
diphenhydramine hydrochloride
diphenhydramine hydrochloride
diphenhydramine hydrochloride
diphenhydramine hydrochloride preservative free
diphenhydramine hydrochloride preservative free
diphenhydramine laurylsulfate
diphenhydramine laurylsulfate
diphenhydramine methylbromide
diphenhydramine methylbromide
diphenhydramine salicylate
diphenhydramine tannate
diphenhydramine tannate
diphenhydraminum
diphenhydraminum
dreemon
dytuss
etanautine
etanautine
etanautine
fedril
gppe cough expect paed
gppe oral soln
histergan
hydramine
hydramine
medinex
n-(2-(diphenylmethoxy)ethyl)-n,n-dimethylamine
n-(2-(diphenylmethoxy)ethyl)-n,n-dimethylamine
nautamine
nightcalm
nytol
nytol
nytol one-a-night
o-benzhydryldimethylaminoethanol
o-benzhydryldimethylaminoethanol
paxidorm
probedryl
silphen
silphen
sleepia
sm-1
sominex
sominex
sominex
syntedril
syntedril
tixylix catarrh
vicks formula 44
vicks formula 44
β-dimethylaminoethyl benzhydryl ether
β-dimethylaminoethyl benzhydryl ether

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT07285031	N/A	Dec 31, 2025	University of British Columbia
NCT06910241	Phase 3	Jul 1, 2025	Baptist Health, Florida Atlantic University
NCT06702670	Phase 2/Phase 3 (Phase 3)	Dec 1, 2024	University of Texas at Houston
NCT06704620	Phase 3	Nov 30, 2024	Tianjin Medical University
NCT06356571	Phase 2	Nov 17, 2024	Sanofi
NCT06819774	Phase 3	Apr 22, 2024	Shandong New Time Pharmaceutical Co., LTD
NCT06345261	N/A	Apr 1, 2024	Cairo University
NCT06043323	Phase 2	Mar 31, 2024	University of Texas at Houston
NCT05896228	Phase 2	Mar 1, 2024	Bristol-Myers Squibb, University of Miami
NCT06207305	Phase 1/Phase 2 (Phase 2)	Jan 30, 2024	University of Texas at Houston
NCT06070649	Phase 1	Jan 17, 2024	National Institute on Alcohol Abuse and Alcoholism (NIAAA), Yale University
NCT06083571	Phase 2	Jan 1, 2024	Washington University in St. Louis
NCT06217367	Phase 4	Dec 5, 2023	Lakehead University
NCT06243185	Phase 2	Nov 17, 2023	Chinese Academy of Medical Sciences
NCT06019728	Phase 4	Nov 10, 2023	Sanofi
NCT05977998	Phase 2	Sep 8, 2023	University of Texas at Houston
NCT06182098	N/A	Jun 27, 2023	Dayton Children's Hospital
NCT05729555	Phase 1	Apr 3, 2023	Guangzhou Kangqi Medical Technology Co., LTD, Overseas Pharmaceuticals, Ltd.
NCT05627557	Phase 3	Feb 28, 2023	Roche
NCT05676216	N/A	Jan 7, 2023	National Taiwan University

Showing 20 of 201 trials

Page 1 / 11

Organizations

Research & Development (158)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
Sanofi	For profit	14	9	4	2004
University of Texas at Houston	Academic/Hospital	12	11	3	2001
Roche	For profit	10	8	3	2004
National Cancer Institute (NCI)	Government	8	4	4	2002
National Institute of Allergy and Infectious Diseases (NIAID)	Government	8	8	3	1999
Yeshiva University	Academic/Hospital	8	8	4	2007
Bayer	For profit	7	7	3	2008
Genentech	For profit	7	6	2	2005
Johnson and Johnson	For profit	6	6	3	2006
National Institutes of Health (NIH)	Government	5	0	2	2002
Pfizer	For profit	5	2	5	2008
GlaxoSmithKline	For profit	4	1	3	2004
University of California, San Francisco	Academic/Hospital	4	0	2	2014
Ache Laboratorios Farmaceuticos S.A.	For profit	3	3	1	2011
Bristol-Myers Squibb	For profit	3	0	1	2015
Immune Tolerance Network	Academic/Hospital	3	0	1	2003
JDP Therapeutics, Inc.	For profit	3	3	2	2013
Mayo Clinic	Academic/Hospital	3	2	3	2007
McNeil	For profit	3	0	2	2006
Northwestern University	Academic/Hospital	3	2	2	2010

158 organizations

Page 1 / 8

Marketing (79)

Organization	Org type	Relationship	Date
Abraxis	For profit	MKTG	May 28, 2002
Actavis	For profit	MKTG	Jan 25, 2019
Akorn, Inc.	For profit	MKTG	Sep 28, 1990
Alpharma	For profit	MKTG	—
Alta Pharma	For profit	MKTG	May 31, 1972
American Cyanamid	For profit	MKTG	Mar 2, 1982
American Home Products	For profit	MKTG	Aug 7, 1972
Amneal Pharmaceuticals	For profit	MKTG	Oct 23, 2018
Anabolic Pharma	Academic/Hospital	MKTG	—
Apotex	For profit	SYN	Aug 22, 2019
Apotex	For profit	MKTG	Aug 22, 2019
Aurobindo Pharma	For profit	MKTG	Feb 14, 2019
Aurobindo Pharma	For profit	SYN	May 31, 2022
Barr Laboratories	For profit	MKTG	Aug 24, 1972
Bausch Health Companies	For profit	MKTG	Jan 18, 1974
Bayer	For profit	MKTG	Jan 17, 2014
Bayer	For profit	NDA2	Jan 17, 2014
Belmar Pharmacy	For profit	MKTG	Jan 25, 1979
Bionpharma Inc	For profit	MKTG	Nov 22, 2010
Bionpharma Inc	For profit	SYN	Nov 22, 2010
Bundy	For profit	MKTG	—
Corepharma	For profit	MKTG	Aug 22, 2019
Cumberland Pharmaceuticals	For profit	MKTG	—
Dow Chemical	For profit	MKTG	—
Dr. Reddy's Laboratories	For profit	SYN	Jul 8, 2009
Dr. Reddy's Laboratories	For profit	MKTG	Jan 29, 1974
Elkins Sinn	For profit	MKTG	—
Eurohlth Intl Sarl	For profit	MKTG	Oct 12, 1973
Fondazione Golgi Cenci	Academic/Hospital	MKTG	—
Forest Laboratories	For profit	MKTG	Apr 28, 1954
Forest Laboratories	For profit	NDA2	Apr 28, 1954
Fosun	For profit	MKTG	Nov 3, 1972
Fresenius	For profit	MKTG	Mar 26, 2013
GlaxoSmithKline	For profit	NDA2	Dec 21, 2005
Granules India	For profit	SYN	Sep 24, 2020
Granules India	For profit	MKTG	Sep 24, 2020
Halsey	For profit	MKTG	Oct 3, 1983
Heather Pharma	For profit	MKTG	—
Heritage Pharma	For profit	MKTG	Aug 24, 1972
Hi Tech Pharmaceuticals	For profit	MKTG	Sep 28, 1990
Hikma	For profit	MKTG	Oct 25, 1973
Hospira	For profit	MKTG	Nov 20, 1998
Impax Laboratories	For profit	MKTG	Nov 14, 1973
International Medication	For profit	MKTG	Mar 15, 1976
LNK International	For profit	MKTG	Jan 27, 1983
Lannett Company, Inc.	For profit	MKTG	Feb 13, 1974
Lederle	For profit	MKTG	Mar 2, 1982
Lumara Health	For profit	MKTG	Sep 22, 1977
Lyphomed, Inc.	For profit	MKTG	Mar 31, 1981
MK Labs	For profit	MKTG	Jan 12, 1973
McNeil	For profit	NDA2	Mar 4, 1946
McNeil	For profit	SYN	Mar 4, 1946
Micro Labs Ltd India	For profit	MKTG	Aug 22, 2018
Morton Grove Pharmaceuticals	For profit	MKTG	Sep 18, 1991
Mutual Pharmaceutical	For profit	MKTG	Dec 19, 1974
Mylan	For profit	MKTG	Jul 12, 2005
Naska Pharmacal	For profit	MKTG	—
Newtron Pharmaceuticals	For profit	MKTG	Feb 8, 1979
Nexgen Pharma, Inc	For profit	MKTG	Oct 12, 1973
P&L Development	For profit	MKTG	Jan 25, 2019
Parke-Davis	For profit	NDA	Jun 1, 1951
Perrigo	For profit	MKTG	May 10, 2019
Pfizer	For profit	MKTG	Dec 21, 2005
Pharmaceutical Associates	For profit	MKTG	Feb 10, 1982
Puracap Pharmaceutical	For profit	MKTG	Jan 25, 1982
Roxane Laboratories	For profit	MKTG	Dec 20, 1972
Strides Pharma Science	For profit	MKTG	Mar 5, 2012
Sun Pharmaceuticals	For profit	MKTG	Jan 2, 1987
Superpharm	For profit	MKTG	—
Teva	For profit	SYN	May 9, 1972
Teva	For profit	MKTG	Oct 30, 1979
Teva	For profit	SYN	Jan 29, 1974
Upsher-Smith Laboratories	For profit	MKTG	Feb 26, 1979
Vanguard	For profit	MKTG	Dec 7, 1981
Warner Chilcott	For profit	MKTG	—
Watson Pharmaceuticals	For profit	MKTG	Sep 27, 1972
West-Ward Pharmaceutical	For profit	MKTG	Nov 27, 1972
Whiteworth Towne Paulsen	For profit	MKTG	Aug 13, 1973
Wockhardt	For profit	MKTG	Oct 12, 1984