diphenoxylate

Small moleculeapproved

Approved

Sep 15, 1960

Diphenoxylate is an opioid drug used for the treatment of acute diarrhea. The drug is used in combination with atropine and marketed under names Lomotil and Diphenoxylate hydrochloride and atropine sulfate. Diphenoxylate is biotransformed in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. The drug exerts its action by activating mu opioid receptors of intestinal mucosa. — NCATS

Clinical trial activity

2 trials · 3 clinical orgs · 43 marketing orgs

Phase 1

Phase 2

Phase 3

Phase 4

Earliest trial started Feb 1, 2003 (NCT00583323)

Timeline

1960s

Sep 15, 1960
Pfizer — Earliest FDA Approval
Sep 15, 1960
G D Searle — NDA Secondary Org
Sep 15, 1960
Pfizer — NDA Secondary Org
Sep 15, 1960
Pfizer — NDA Organization

1970s

Apr 18, 1977
MD Pharma — Marketing Organization
Jun 3, 1977
Sun Pharmaceuticals — Marketing Organization
Jun 7, 1977
Fosun — Marketing Organization
Jul 5, 1977
R&S Pharma — Marketing Organization
Nov 17, 1977
Mylan — Marketing Organization
Jan 27, 1978
Lumara Health — Marketing Organization
Feb 13, 1978
Medpointe — Marketing Organization
Feb 21, 1978
Lannett Company, Inc. — Marketing Organization
Mar 9, 1978
Inwood Laboratories — Marketing Organization
Jun 22, 1978
Watson Pharmaceuticals — Marketing Organization
Oct 29, 1979
Ani Pharmaceuticals — Marketing Organization

1980s

Apr 6, 1981
R.P. Scherer — Marketing Organization
Jul 17, 1981
Parke-Davis — Marketing Organization
Jul 17, 1981
Warner Lambert — Marketing Organization
Mar 29, 1982
Upsher-Smith Laboratories — Marketing Organization
May 3, 1982
Hikma — Marketing Organization
Sep 9, 1982
Lederle — Marketing Organization
Sep 9, 1982
American Cyanamid — Marketing Organization
Mar 25, 1983
Vanguard — Marketing Organization
May 10, 1985
Superpharm — Marketing Organization

1990s

Mar 5, 1997
Bausch Health Companies — Marketing Organization

2000s

May 2, 2000
Par Pharmaceuticals — Marketing Organization
May 2, 2000
Strides Pharma Science — Marketing Organization
Nov 27, 2000
Able Laboratories — Marketing Organization
Jan 1, 2003
Earliest Phase 3 Sponsor(trial)

2010s

Nov 13, 2018
Bayshore Pharms Llc — Marketing Organization
Nov 13, 2018
IPCA Laboratories Ltd. — Marketing Organization
Nov 13, 2018
Unichem — Marketing Organization

2020s

Feb 20, 2020
Leading Pharma Llc — Marketing Organization
Jun 3, 2020
Mayne Pharma — Marketing Organization
Jun 3, 2020
Dr. Reddy's Laboratories — Marketing Organization
Oct 6, 2020
Specgx Llc — Marketing Organization
Oct 6, 2020
Mallinckrodt (2013) — Marketing Organization
Oct 21, 2020
Chartwell Pharmaceuticals — Marketing Organization
Oct 21, 2020
Pharma Life Sciences LLC — Marketing Organization
Oct 21, 2020
Eci Pharmaceuticals Llc — Marketing Organization
Jan 27, 2021
Winder Labs Llc — Marketing Organization

Indications

Approved for

Diarrhea (approved 1960)

Studied for

Mechanism of action

Mu opioid receptorAGONIST
OPRM agonist
- Mu-type opioid receptor (OPRM) ↗

Combination products

lomotil
with atropine
Also known as colonai, di-atro, logen, lonox, lo-trol

Approval history

approvedPriority reviewSep 15, 1960

Chemistry & pharmacology

Loading structure…

SMILES

CCOC(=O)C1(c2ccccc2)CCN(CCC(C#N)(c2ccccc2)c2ccccc2)CC1

Mol. weight: 452.6 g/mol
Lipinski Ro5: 1 violation(s)
Rule of 3: No
Chirality: Achiral Molecule
Inorganic: No
Polymer: No
Delivery: Oral
Availability: Prescription Only

Oral

Yes

Parenteral

Topical

Sources

Also known as

1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotic acid ethyl ester
1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-isonipecotic acid ethyl ester
2,2-diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile
2,2-diphenyl-4-(4-carbethoxy-4-phenylpiperidino)butyronitrile
4-ethoxycarbonyl-alpha,alpha,4-triphenyl-1-piperidinebutyronitrile
4-ethoxycarbonyl-alpha,alpha,4-triphenyl-1-piperidinebutyronitrile
4-piperidinecarboxylic acid, 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-, ethyl ester, monohydrochloride, mixt. with endo-(+-)-8-methyl-8-azabicyclo(3.2.1)oct-3-yl alpha-(hydroxymethyl)benzeneacetate sulfate (2:1) (salt)
atropine sulfate - diphenoxylate hydrochloride
atropine sulfate-diphenoxylate hydrochloride drug combination
difenossilato
difenossilato
difenoxilato
difenoxilato
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate
diphenoxylate hcl
diphenoxylate hcl
diphenoxylate hcl
diphenoxylate hydrochloride
diphenoxylate hydrochloride
diphenoxylate hydrochloride
diphenoxylatum
diphenoxylatum
ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate
ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidinecarboxylate
ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate
ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate
lomotil
lomotil
lomotil
reasec

Clinical trials

NCT ID	Phase	Start date	Sponsor(s)
NCT02666014	Phase 3	Jun 1, 2015	Government of Singapore, KK Women's and Children's Hospital
NCT00583323	Phase 3	Feb 1, 2003	Mayo Clinic

Showing 2 of 2 trials

Page 1 / 1

Organizations

Research & Development (3)

Organization	Org type	Trials	As lead sponsor	Phases	Earliest year
Government of Singapore	Government	1	0	1	2015
KK Women's and Children's Hospital	Academic/Hospital	1	1	1	2015
Mayo Clinic	Academic/Hospital	1	1	1	2003

3 organizations

Page 1 / 1

Marketing (49)

Organization	Org type	Relationship	Date
Able Laboratories	For profit	MKTG	Nov 27, 2000
Alpharma	For profit	MKTG	—
American Cyanamid	For profit	MKTG	Sep 9, 1982
Ani Pharmaceuticals	For profit	MKTG	Oct 29, 1979
Ani Pharmaceuticals	For profit	MKTG	Oct 29, 1979
Ascot Pharmaceuticals	For profit	MKTG	—
Bausch Health Companies	For profit	MKTG	Mar 5, 1997
Bayshore Pharms Llc	For profit	MKTG	Nov 13, 2018
Chartwell Pharmaceuticals	For profit	MKTG	Oct 21, 2020
Dr. Reddy's Laboratories	For profit	MKTG	Jun 3, 2020
Eci Pharmaceuticals Llc	For profit	MKTG	Oct 21, 2020
Fosun	For profit	MKTG	Jun 7, 1977
G D Searle	For profit	NDA2	Sep 15, 1960
Halsey	For profit	MKTG	—
Heather Pharma	For profit	MKTG	—
Hikma	For profit	MKTG	May 3, 1982
Hikma	For profit	SYN	Mar 15, 1982
IPCA Laboratories Ltd.	For profit	MKTG	Nov 13, 2018
Inwood Laboratories	For profit	MKTG	Mar 9, 1978
Lannett Company, Inc.	For profit	MKTG	Feb 21, 1978
Leading Pharma Llc	For profit	MKTG	Feb 20, 2020
Leading Pharma Llc	For profit	SYN	Feb 20, 2020
Lederle	For profit	MKTG	Sep 9, 1982
Lumara Health	For profit	MKTG	Jan 27, 1978
MD Pharma	For profit	MKTG	Apr 18, 1977
Mallinckrodt (2013)	For profit	MKTG	Oct 6, 2020
Mayne Pharma	For profit	MKTG	Jun 3, 2020
Medpointe	For profit	MKTG	Feb 13, 1978
Mylan	For profit	MKTG	Nov 17, 1977
Mylan	For profit	SYN	Dec 22, 1978
Par Pharmaceuticals	For profit	MKTG	May 2, 2000
Parke-Davis	For profit	MKTG	Jul 17, 1981
Pfizer	For profit	NDA2	Sep 15, 1960
Pfizer	For profit	NDA	Sep 15, 1960
Pharma Life Sciences LLC	For profit	MKTG	Oct 21, 2020
R&S Pharma	For profit	MKTG	Jul 5, 1977
R.P. Scherer	For profit	MKTG	Apr 6, 1981
Roxane Laboratories	For profit	MKTG	—
Specgx Llc	For profit	MKTG	Oct 6, 2020
Strides Pharma Science	For profit	MKTG	May 2, 2000
Sun Pharmaceuticals	For profit	MKTG	Jun 3, 1977
Superpharm	For profit	MKTG	May 10, 1985
Unichem	For profit	MKTG	Nov 13, 2018
Upsher-Smith Laboratories	For profit	MKTG	Mar 29, 1982
Upsher-Smith Laboratories	For profit	SYN	Aug 31, 2018
Vanguard	For profit	MKTG	Mar 25, 1983
Warner Lambert	For profit	MKTG	Jul 17, 1981
Watson Pharmaceuticals	For profit	MKTG	Jun 22, 1978
Winder Labs Llc	For profit	MKTG	Jan 27, 2021