U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C30H32N2O2
Molecular Weight 452.5884
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENOXYLATE

SMILES

CCOC(=O)C1(CCN(CC1)CCC(C#N)(c2ccccc2)c3ccccc3)c4ccccc4

InChI

InChIKey=HYPPXZBJBPSRLK-UHFFFAOYSA-N
InChI=1S/C30H32N2O2/c1-2-34-28(33)29(25-12-6-3-7-13-25)18-21-32(22-19-29)23-20-30(24-31,26-14-8-4-9-15-26)27-16-10-5-11-17-27/h3-17H,2,18-23H2,1H3

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including ISBN-13: 978-0323055932

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.

CNS Activity

CNS Active
3730
Curator's Comment:: At high doses it exhibits codeine-like subjective effects.

Originator

Approval Year

1960
96
Targets

Targets

Primary TargetPharmacologyConditionPotency
Mu-type opioid receptor
54
Target ID: P35372|||G8XRH8|||Q5TDA1|||Q9UN57
Gene ID: 4988.0
Gene Symbol: OPRM1
Target Organism: Homo sapiens (Human)
Sources: ISBN-13: 978-0323055932
Agonist
2470
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8043
LOMOTIL

Approved Use

Lomotil is effective as adjunctive therapy in the management of diarrhea.

Launch Date

-2.93414404E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
622.68 ng/mL
EXPERIMENT
https://www.researchgate.net/publication/254338105_Determination_of_diphenoxylate_in_rat_plasma_by_gradient_elution_LC-ESI-MS
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENOXYLATE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/5026379
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENOXYLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
7157.61 ng × h/mL
EXPERIMENT
https://www.researchgate.net/publication/254338105_Determination_of_diphenoxylate_in_rat_plasma_by_gradient_elution_LC-ESI-MS
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENOXYLATE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.68 h
EXPERIMENT
https://www.researchgate.net/publication/254338105_Determination_of_diphenoxylate_in_rat_plasma_by_gradient_elution_LC-ESI-MS
10 mg/kg single, oral
dose: 10 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENOXYLATE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/5026379
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DIPHENOXYLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
15.5%
OTHER
https://go.drugbank.com/drugs/DB01081
DIPHENOXYLATE unknown
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day steady, oral
Studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: steady
Dose: 20 mg, 1 times / day
Co-administed with::
atropine sulfate(0.025 mg)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
300 mg 1 times / day steady, oral (max)
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
Other AEs: Drug dependence...
Other AEs:
Drug dependence
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Drug dependence
300 mg 1 times / day steady, oral (max)
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/012462s048lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inducer
707

inhibitor
1467
inducer
355
inducer
97

inhibitor
1702
inhibitor
1475

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Ca2+ channels
40

CYP2B6
717
P-gp
1400
CYP2C19
269

CYP1A2
637

CYP2B6
501
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
1392
 minor
yes (co-administration study)
Comment: diphenoxylate decreased omeprazole AUC and Cmax
Page: abstract
CYP2B6
884
 no
CYP2D6
1738
 no
CYP3A4
1772
 no
CYP2B6
884
 no
no (co-administration study)
Comment: diphenoxylate had no effect on buproprion AUC and Cmax
Page: 18805.0
CYP2D6
1738
 no
no (co-administration study)
Comment: diphenoxylate had no effect on metroprolol AUC and Cmax
Page: 18805.0
CYP3A4
1772
 no
no (co-administration study)
Comment: diphenoxylate had no effect on testosterone AUC and Cmax
Page: 18805.0
Ca2+ channels
43
 unlikely
CYP1A2
1532
 yes
yes (co-administration study)
Comment: diphenoxylate decreased phenacetin AUC and Cmax
Page: abstract
CYP2C9
1648
 yes
yes (co-administration study)
Comment: diphenoxylate decreased tolbutamide AUC and Cmax
Page: abstract
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1400
 no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1507
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4639
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4639
ChemicalBook
CB3301641
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3301641
ZINC
ZINC000003830716
http://zinc15.docking.org/substances/ZINC000003830716
PubMed

PubMed

TitleDatePubMed
Antidiarrhoeal effects of methanolic root extract of Hemidesmus indicus (Indian sarsaparilla)--an in vitro and in vivo study.
2003 Apr
Management of acute cancer treatment-induced diarrhea.
2003 Nov
Medical management of fecal incontinence.
2004 Jan
Protective effect of Arque-Ajeeb on acute experimental diarrhoea in rats.
2004 Jul 6
A randomized controlled trial of mycophenolate mofetil in patients with IgA nephropathy [ISRCTN62574616].
2004 Mar 25
The clinical and pathologic significance of microscopic colitis.
2004 May-Jun
Deadly pediatric poisons: nine common agents that kill at low doses.
2004 Nov
[Treatment of 64 cases with compound diphenoxylate poisoning with naloxone].
2004 Sep
Acute anticholinergic poisoning in children.
2005 Dec
Comparison between prospective and retrospective evaluation of Crohn's disease activity index.
2005 May
Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?
2005 May 10
Lomotil dependence: a note of caution.
2005 Nov-Dec
Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.
2005 Oct
Evaluation of antimotility effect of Lantana camara L. var. acuelata constituents on neostigmine induced gastrointestinal transit in mice.
2005 Sep 17
Guidelines for the diagnosis and management of carcinoid tumours. Part 1: the gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group.
2006 Apr
Long-acting octreotide in the treatment of diarrhea after pelvic pouch surgery.
2006 Dec
Treatment of diarrhea in patients with inflammatory bowel disease: concepts and cautions.
2007
Loperamide: a pharmacological review.
2007
[Treating travelers' diarrhea. When should medication be given?].
2007 Dec
Prevention and management of chemotherapy-induced diarrhea in patients with colorectal cancer: a consensus statement by the Canadian Working Group on Chemotherapy-Induced Diarrhea.
2007 Feb
Diphenoxylate hydrochloride dependency.
2007 Jul
Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis.
2007 Mar 27
Pharmacotherapy for fecal incontinence: a review.
2007 May
Myasthenia gravis.
2007 Nov 6
Drug-induced diarrhea.
2007 Oct
In vivo evaluation of antidiarrhoeal activity of Rhus semialata fruit extract in rats.
2007 Oct 27
Methylnaltrexone in the treatment of opioid-induced constipation.
2008
Toward achieving optimal response: understanding and managing antidepressant side effects.
2008
Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers.
2008 Jan
Anticholinergic activity of 107 medications commonly used by older adults.
2008 Jul
[Methodological study on quality evaluation of rhubarb based on purgative bioassay].
2008 Jun
[Topic: Treating travelers' diarrhea. When should medication be given?].
2008 Jun
Long-term outcome of in-patients with substance use disorders: A study from North India.
2008 Oct
Antimotility agents for chronic diarrhoea in people with HIV/AIDS.
2008 Oct 8
The role of loperamide in gastrointestinal disorders.
2008 Winter
Hashish body packing: a case report.
2009
Bowel management for the treatment of pediatric fecal incontinence.
2009 Dec
Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma.
2009 Feb 18
[Roles of enteric nervous system neurotransmitters and interstitial cells of Cajal in the colon in slow transit constipation in rats].
2009 Jun
Pharmacokinetic drug interactions of synthetic opiate analgesics.
2009 Mar-Apr
Pretreatment with diphenoxylate hydrochloride/atropine sulfate (Lomotil) does not decrease physiologic bowel FDG activity on PET/CT scans of the abdomen and pelvis.
2009 Mar-Apr
Managing toxicities and optimal dosing of targeted drugs in advanced kidney cancer.
2009 May
An Open-Label, Noncomparative, Multicenter Study to Evaluate Efficacy and Safety of NASHA/Dx Gel as a Bulking Agent for the Treatment of Fecal Incontinence.
2010
Re: "Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers".
2010 Apr
Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.
2010 Apr 7
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Antidiarrhoeal activity of carbazole alkaloids from Murraya koenigii Spreng (Rutaceae) seeds.
2010 Jan
Lymphocytic colitis presenting as difficult diarrhoea in an African woman: a case report and review of the literature.
2010 Jan 29
Antidiarrheal activity of extracts and compound from Trilepisium madagascariense stem bark.
2010 Jun
Effect of an antidiabetic polysaccharide from Inula japonica on constipation in normal and two models of experimental constipated mice.
2010 Nov
Patents

Patents

JP2009526755A
410

Sample Use Guides

In Vivo Use Guide
Adults: The recommended initial dosage is two Lomotil tablets (each tablet contains 2,5 mg diphenoxylate hydrochloride) four times daily; Dosage schedule for children: The recommended initial total daily dosage of Lomotil liquid for children is 0.3 to 0.4 mg/kg, administered in four divided doses.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
DIPHENOXYLATE
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
DIPHENOXYLATE [INN]
Common Name English
ISONIPECOTIC ACID, 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYL-, ETHYL ESTER
Common Name English
DIPHENOXYLATE [MI]
Common Name English
DIPHENOXYLATE [VANDF]
Common Name English
DIPHENOXYLATE [HSDB]
Common Name English
1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYLPIPERIDINE-4-CARBOXYLIC ACID ETHYL ESTER
Systematic Name English
DIPHENOXYLATE [WHO-DD]
Common Name English
IDS-ND-016
Code English
4-PIPERIDINECARBOXYLIC ACID, 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYL-, ETHYL ESTER
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000178374
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
NCI_THESAURUS C266
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
WHO-ATC A07DA01
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
LIVERTOX 315
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
WHO-VATC QA07DA01
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
DEA NO. 9170
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
Code System Code Type Description
PUBCHEM
13505
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
CAS
915-30-0
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
DRUG CENTRAL
918
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
NCI_THESAURUS
C62024
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
DRUG BANK
DB01081
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
MESH
D004157
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
LACTMED
Diphenoxylate
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
HSDB
3067
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201294
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PRIMARY
IUPHAR
7164
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
EPA CompTox
915-30-0
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
INN
850
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
MERCK INDEX
M4613
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY Merck Index
FDA UNII
73312P173G
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
ECHA (EC/EINECS)
213-020-1
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
EVMPD
SUB07212MIG
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
RXCUI
3500
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
DIPHENOXYLATE
Created by admin on Sat Jun 26 11:27:24 UTC 2021 , Edited by admin on Sat Jun 26 11:27:24 UTC 2021
PRIMARY
ACTIVE MOIETY
Structure of DIPHENOXYLATE
METABOLITE (PARENT)
Structure of DIFENOXIN
SALT/SOLVATE (PARENT)
Structure of DIPHENOXYLATE HYDROCHLORIDE
NIH
NCATS
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