theophylline

Trade name: synophylate

Small moleculeapproved

Approved

Oct 17, 1947

Since its discovery as component of the tea leaf by Albert Kossel in 1888, the history of theophylline (CAS 58-55-9) has been a long and successful one. At the turn of the century, theophylline became less expensive due to chemical synthesis and was primarily used as diuretic in subsequent years. It was Samuel Hirsch who discovered the bronchospasmolytic effect of theophylline in 1992, however, despite this pioneering discovery theophylline continued to be used primarily as diuretic and cardiac remedy. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Theophylline is indicated for the treatment of acute exacerbations of the symptoms and reversible airflow obstruction associated with asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis. — NCATS

Clinical trial activity

70 trials · 84 clinical orgs · 59 marketing orgs

Phase 1

Phase 2

Phase 3

Phase 4

Earliest trial started Apr 1, 1994 (NCT00000578)

Timeline

1940s

Oct 17, 1947
Central Pharmacal — Earliest FDA Approval
Oct 17, 1947
Central Pharmacal — NDA Organization
Oct 17, 1947
Century Pharmaceuticals — NDA Secondary Org

1970s

Nov 21, 1970
Precision Dose — Marketing Organization
Feb 8, 1979
Halsey — Marketing Organization
Mar 26, 1979
3M — Marketing Organization
Apr 12, 1979
Schering — Marketing Organization
Apr 12, 1979
Schering-Plough — Marketing Organization
May 15, 1979
Sanofi-Aventis — Marketing Organization
Jul 13, 1979
Lumara Health — Marketing Organization

1980s

Jan 30, 1980
Wockhardt — Marketing Organization
May 30, 1980
Medicis — Marketing Organization
Jun 25, 1980
Pharmaceutical Associates — Marketing Organization
Aug 11, 1980
Century Pharmaceuticals — Marketing Organization
Nov 14, 1980
Johnson and Johnson — Marketing Organization
Sep 17, 1981
Graham Dm — Marketing Organization
Apr 15, 1982
Fondazione Golgi Cenci — Marketing Organization
Jul 26, 1982
Baxalta — NDA Secondary Org
Jul 26, 1982
Baxter — NDA Secondary Org
Sep 1, 1982
Rhodes Pharmaceuticals, L.P. — Marketing Organization
Jan 11, 1983
Nostrum Laboratories — Marketing Organization
Jun 21, 1983
Monarch Pharmaceuticals — Marketing Organization
Aug 17, 1983
Pharmaceutical Research Associates, Inc. (PRA) — Marketing Organization
Aug 22, 1983
Actient — Marketing Organization
Sep 15, 1983
Roxane Laboratories — Marketing Organization
Sep 15, 1983
Boehringer Ingelheim — Marketing Organization
Nov 7, 1984
B. Braun — NDA Secondary Org
Dec 14, 1984
Hospira — NDA Secondary Org
Mar 20, 1985
UCB — Marketing Organization
Apr 3, 1985
Forest Laboratories — Marketing Organization
Oct 9, 1985
Sandoz — Marketing Organization
Jun 12, 1986
R.P. Scherer — Marketing Organization
Nov 24, 1986
Fleming Pharmaceuticals — Marketing Organization
Oct 28, 1988
Taro Pharmaceuticals — Marketing Organization
Oct 4, 1989
Alpharma — Marketing Organization

1990s

Apr 30, 1990
Heritage Pharma — Marketing Organization
Feb 28, 1992
Auxillium — Marketing Organization
Jan 1, 1994
Earliest Phase 3 Sponsor(trial)
Feb 14, 1994
Inwood Laboratories — Marketing Organization
Mar 14, 1997
International Minerals and Chemical Corporation — Marketing Organization
Jan 1, 1998
Boehringer Ingelheim — Earliest Phase 1 Sponsor(trial)
Jan 1, 1999
Earliest Phase 2 Sponsor(trial)

2000s

Apr 27, 2004
Able Laboratories — Marketing Organization
Apr 21, 2006
Mylan — Marketing Organization

2010s

Jul 13, 2010
Glenmark Pharmaceuticals — Marketing Organization
Oct 27, 2010
Alembic — Marketing Organization
Apr 13, 2011
Lannett Company, Inc. — Marketing Organization
Apr 13, 2011
Chartwell Pharmaceuticals — Marketing Organization
Jun 15, 2012
Tris Pharma, Inc. — Marketing Organization

2020s

Oct 12, 2022
Teva — Marketing Organization
Jan 30, 2023
Leading Pharma Llc — Marketing Organization
Mar 20, 2023
Amneal Pharmaceuticals — Marketing Organization
Apr 26, 2023
Bionpharma Inc — Marketing Organization
Sep 8, 2023
Annora Pharma — Marketing Organization
Oct 24, 2023
Harman Finochem — Marketing Organization

Indications

Approved for

Studied for

Mechanism of action

Adenosine receptorANTAGONIST
Adenosine receptor antagonist
Phosphodiesterase 4INHIBITOR
Phosphodiesterase 4 inhibitor
Phosphodiesterase 3INHIBITOR
Phosphodiesterase 3 inhibitor
- cGMP-inhibited 3',5'-cyclic phosphodiesterase A (PDE3A) ↗
- cGMP-inhibited 3',5'-cyclic phosphodiesterase B (PDE3B) ↗
- Phosphodiesterase 3A
- Phosphodiesterase 3B
Histamine H1 receptorANTAGONIST
Histamine H1 receptor antagonist
- Histamine H1 receptor (HRH1) ↗
Unspecified targetOTHER
Unknown
Theophylline is a bronchodilator by relaxing brochial smooth muscle, oppose the effects of many broncho-constrictor mediators, and also relaxes smooth muscle in the urinary and biliary ways.

Combination products

dicurin procaine
with procaine merethoxylline
mersalyl-theophylline
with sodium mersalyl

Approval history

approvedOct 17, 1947

Chemistry & pharmacology

Loading structure…

SMILES

CN1C2=C(N=CN2)C(=O)N(C)C1=O

Mol. weight: 180.164 g/mol
Lipinski Ro5: Pass
Rule of 3: No
Chirality: Achiral Molecule
Inorganic: No
Polymer: No
Delivery: Oral
Availability: Discontinued

Oral

Yes

Parenteral

Topical

Sources

Also known as

1-(3-(4-(diphenylmethyl)-1-piperazinyl)propyl)-1,3-dihydro-2h-benzimidazol-2-one
1,3-dimethyl-7h-purine-2,6-dione
1,3-dimethyl-7h-purine-2,6-dione
1,3-dimethylxanthine
1,3-dimethylxanthine
1,3-dimethylxanthine
1-benzylethylamine
(+/-)-1-phenyl-2-aminopropane
7-theophyllineacetic acid
accurbron
accurbron
acefylline
acefylline
acefylline
acefylline
acefylline
acefylline piperazine
acefylline piperazine
acefylline piperazine
acefylline piperazine
acefylline piperazine salt
acefylline, sodium salt
acefyllin piperazinate
acephylline
acephylline
acephylline
acephylline
acephylline piperazinate
acepifylline
acepifylline
acepifylline
acepifylline
acepiphyllin
aerolate
aerolate
aerolate iii
aerolate iii
aerolate jr
aerolate jr
aerolate sr
aerolate sr
aethaphyllinum
ambuphylline
aquaphyllin
aquaphyllin
asbron
asbron
bronkodyl
bronkodyl
bufylline
bufylline
bufylline
bufylline
butaphyllamine
carboxymethyltheophylline
celtect
celtomide
dimethylxanthine
dimethylxanthine
duraphyl
duraphyl
elixicon
elixicon
elixomin
elixomin
elixophyllin
elixophyllin
elixophyllin
elixophyllin sr
elixophyllin sr
etaphylline
etophylate
etophylate
fenethylene
fenethylline
fenethylline hcl
fenethylline hydrochloride
fenethylline hydrochloride
fenethylline hydrochloride
fenethylline hydrochloride
fenethylline hydrochloride
fenetyllin
fenetylline
fenetylline
kw 4354
kw-4354
kw-4354
kw-4354
kw-4354
kw-4354
labid
labid
lanophyllin
lanophyllin
lanophyllin
lasma
lasma
minophylline
nuelin
nuelin
nuelin sa
nuelin sa
nuelin sa-250
oxatimide
oxatomide
oxatomide
oxatomide
oxatomide
oxatomide
oxatomide
oxatomide
phenedrine
phenethylline
piperazine theophylline ethanoate
piperazine theophylline ethanoate
piperazine theophylline ethanoate
pro-vent
pro-vent
quibron
quibron
quibron-t
quibron-t
quibron-t/sr
quibron-t/sr
r35443
r 35443
r 35 443
r-35443
r-35443
respbid
respbid
slo-bid
slo-bid
slo-phyllin
slo-phyllin
sustaire
sustaire
synophylate
synophylate
synophylate
theo-24
theo-24
theobid
theobid
theobid jr.
theobid jr.
theochron
theochron
theocin
theocin
theoclear-100
theoclear-100
theoclear-200
theoclear-200
theoclear-80
theoclear-80
theoclear l.a.-130
theoclear l.a.-130
theoclear l.a.-260
theoclear l.a.-260
theo-dur
theo-dur
theograd
theograd
theolair
theolair
theolair-sr
theolair-sr
theolixir
theolixir
theophyl
theophyl
theophyl-225
theophyl-225
theophyllin
theophyllin
theophyllin
theophyllin-7-acetic acid piperazine salt
theophylline
theophylline
theophylline
theophylline
theophylline
theophylline
theophylline
theophylline
theophylline
theophylline-7-acetic acid
theophyllineacetic acid
theophylline aminoisobutanol
theophylline anhydrous
theophylline anhydrous
theophylline anhydrous
theophylline, anhydrous
theophylline, anhydrous
theophylline ethanoate of piperazine
theophyllineethylamphetamine
theophylline glycinate
theophylline glycinate
theophylline sodium glycinate
theophylline sodium glycinate
theophylline sodium glycinate
theophylline sodium glycinate
theophylline-sr
theophylline-sr
theophyl-sr
theophyl-sr
theovent
theovent
tinset
tinset
tinset
t-phyl
t-phyl
uni-dur
uni-dur
uniphyl
uniphyl
uniphyllin continus
uniphyllin continus

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT07015866	N/A	Jul 30, 2025	Chinese University of Hong Kong, The Hong Kong Polytechnic University, University of Derby
NCT06189404	Phase 1	Oct 31, 2023	LG
NCT05853601	Phase 1/Phase 2 (Phase 2)	Oct 17, 2023	Medical College of Wisconsin, University of Oklahoma
NCT05717049	Phase 2	Feb 9, 2023	Norwegian Health Association, South-Eastern Norway Regional Health Authority, University of Oslo
NCT05666219	Phase 4	Dec 19, 2022	Government of Pakistan
NCT05947643	Phase 2	Nov 22, 2022	Washington University in St. Louis
NCT04789499	Phase 2	Mar 15, 2021	Washington University in St. Louis
NCT07171021	Phase 4	Dec 1, 2020	Taichung Veterans General Hospital
NCT04551170	Phase 2	Jul 13, 2020	Vanderbilt University
NCT04269187	Early Phase 1 (Phase 1)	Apr 30, 2020	Assiut University
NCT04309877	Early Phase 1 (Phase 1)	Mar 31, 2020	University of California, Los Angeles
NCT04240821	Phase 2	Mar 30, 2020	Vanderbilt University
NCT03984188	Phase 3	Jan 1, 2020	National Heart, Lung, and Blood Institute (NHLBI), University of Miami
NCT04148846	N/A	Sep 20, 2019	University of Sao Paulo
NCT03894189	N/A	May 31, 2019	Beni Suef University
NCT03990766	Phase 2	May 15, 2019	Washington University in St. Louis
NCT03718403	Phase 4	Apr 10, 2019	Harvard University
NCT04257851	Phase 4	Jan 1, 2019	Damanhour University
NCT03029429	Phase 2	Dec 1, 2017	Harvard University, Vanderbilt University
NCT03269318	Phase 4	Jul 1, 2017	University of Brighton, University of Sussex

Showing 20 of 70 trials

Page 1 / 4

Organizations

Research & Development (84)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
Harvard University	Academic/Hospital	4	2	2	2015
Vanderbilt University	Academic/Hospital	4	4	1	2015
AstraZeneca	For profit	3	3	2	2004
Mutual Pharmaceutical	For profit	3	2	2	2007
National Heart, Lung, and Blood Institute (NHLBI)	Government	3	1	2	1994
Southern Medical University	Academic/Hospital	3	2	1	2013
Washington University in St. Louis	Academic/Hospital	3	3	1	2019
Boehringer Ingelheim	For profit	2	2	1	1998
Guangzhou Medical University	Academic/Hospital	2	2	1	2012
Merck	For profit	2	2	1	2003
Technical University of Munich	Academic/Hospital	2	2	2	2002
University of Miami	Academic/Hospital	2	2	2	2014
Assiut University	Academic/Hospital	1	1	1	2020
Baqiyatallah Medical Sciences University	Academic/Hospital	1	1	1	2008
Beni Suef University	Academic/Hospital	1	1	1	2019
Benxi City hospital of Chinese medicine	Academic/Hospital	1	0	1	2008
Canadian Cancer Trials Group	Academic/Hospital	1	1	1	1998
Canadian Institutes of Health Research (CIHR)	Academic/Hospital	1	0	1	2001
Canadian Lung Association	Academic/Hospital	1	0	1	2006
Changda hospital	Academic/Hospital	1	0	1	2008

84 organizations

Page 1 / 5

Marketing (67)

Organization	Org type	Relationship	Date
3M	For profit	MKTG	Mar 26, 1979
Able Laboratories	For profit	MKTG	Apr 27, 2004
Actient	For profit	MKTG	Aug 22, 1983
Alembic	For profit	MKTG	Oct 27, 2010
Alembic	For profit	SYN	Oct 27, 2010
Alpharma	For profit	MKTG	Oct 4, 1989
Amneal Pharmaceuticals	For profit	MKTG	Mar 20, 2023
Annora Pharma	For profit	MKTG	Sep 8, 2023
Auxillium	For profit	MKTG	Feb 28, 1992
Auxillium	For profit	SYN	Aug 22, 1983
B. Braun	For profit	NDA2	Nov 7, 1984
Baxalta	For profit	NDA2	Jul 26, 1982
Baxter	For profit	NDA2	Jul 26, 1982
Bionpharma Inc	For profit	MKTG	Apr 26, 2023
Boehringer Ingelheim	For profit	MKTG	Sep 15, 1983
Central Pharmacal	For profit	NDA	Oct 17, 1947
Century Pharmaceuticals	For profit	NDA2	Oct 17, 1947
Century Pharmaceuticals	For profit	MKTG	Aug 11, 1980
Chartwell Pharmaceuticals	For profit	MKTG	Apr 13, 2011
Eli Lilly	For profit	NDA2	—
Ferndale Laboratories, Inc.	For profit	MKTG	—
Fisons	For profit	MKTG	—
Fleming Pharmaceuticals	For profit	MKTG	Nov 24, 1986
Fondazione Golgi Cenci	Academic/Hospital	MKTG	Apr 15, 1982
Forest Laboratories	For profit	MKTG	Apr 3, 1985
Glenmark Pharmaceuticals	For profit	MKTG	Jul 13, 2010
Glenmark Pharmaceuticals	For profit	SYN	Jun 3, 2021
Graham Dm	For profit	MKTG	Sep 17, 1981
Halsey	For profit	MKTG	Feb 8, 1979
Harman Finochem	For profit	MKTG	Oct 24, 2023
Heritage Pharma	For profit	MKTG	Apr 30, 1990
Heritage Pharma	For profit	MKTG	Apr 30, 1990
Hospira	For profit	NDA2	Dec 14, 1984
Hospira	For profit	MKTG	—
International Minerals and Chemical Corporation	For profit	MKTG	Mar 14, 1997
Inwood Laboratories	For profit	MKTG	Feb 14, 1994
Johnson and Johnson	For profit	MKTG	Nov 14, 1980
Lannett Company, Inc.	For profit	SYN	Jul 26, 1976
Lannett Company, Inc.	For profit	MKTG	Apr 13, 2011
Leading Pharma Llc	For profit	MKTG	Jan 30, 2023
Lumara Health	For profit	MKTG	Jul 13, 1979
Medicis	For profit	MKTG	May 30, 1980
Monarch Pharmaceuticals	For profit	MKTG	Jun 21, 1983
Mylan	For profit	MKTG	Apr 21, 2006
Nostrum Laboratories	For profit	SYN	Jan 26, 1979
Nostrum Laboratories	For profit	MKTG	Jan 11, 1983
Novartis	For profit	MKTG	—
Panray Corp.	For profit	MKTG	—
Pfizer	For profit	MKTG	—
Pharmaceutical Associates	For profit	MKTG	Jun 25, 1980
Pharmaceutical Research Associates, Inc. (PRA)	For profit	MKTG	Aug 17, 1983
Precision Dose	For profit	MKTG	Nov 21, 1970
R.P. Scherer	For profit	MKTG	Jun 12, 1986
Rhodes Pharmaceuticals, L.P.	For profit	MKTG	Sep 1, 1982
Roxane Laboratories	For profit	MKTG	Sep 15, 1983
Sandoz	For profit	MKTG	Oct 9, 1985
Sanofi-Aventis	For profit	MKTG	May 15, 1979
Schering	For profit	MKTG	Apr 12, 1979
Schering-Plough	For profit	MKTG	Apr 12, 1979
Schwarz Pharma	For profit	MKTG	—
Taro Pharmaceuticals	For profit	MKTG	Oct 28, 1988
Teva	For profit	MKTG	Oct 12, 2022
Tris Pharma, Inc.	For profit	MKTG	Jun 15, 2012
UCB	For profit	MKTG	Mar 20, 1985
Warner Chilcott	For profit	MKTG	—
Watson Pharmaceuticals	For profit	MKTG	—
Wockhardt	For profit	MKTG	Jan 30, 1980