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Details

Stereochemistry ACHIRAL
Molecular Formula C30H32N2O2
Molecular Weight 452.5873
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENOXYLATE

SMILES

CCOC(=O)C1(CCN(CCC(C#N)(C2=CC=CC=C2)C3=CC=CC=C3)CC1)C4=CC=CC=C4

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
3913
Curator's Comment: At high doses it exhibits codeine-like subjective effects.

Originator

Approval Year

1960
107
Targets

Targets

Primary TargetPharmacologyConditionPotency
Mu-type opioid receptor
61
Target ID: P35372|||G8XRH8|||Q5TDA1|||Q9UN57
Gene ID: 4988.0
Gene Symbol: OPRM1
Target Organism: Homo sapiens (Human)
Sources: ISBN-13: 978-0323055932
Agonist
2678
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
LOMOTIL

Approved Use

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

Launch Date

1960
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
781

inhibitor
1587
inducer
389
inducer
97

inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Ca2+ channels
57

CYP2B6
810
P-gp
1537
CYP2C19
293

CYP1A2
701

CYP2B6
547
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
1553
 minor
yes (co-administration study)
Comment: diphenoxylate decreased omeprazole AUC and Cmax
Page: abstract
CYP2B6
1001
 no
CYP2D6
1891
 no
CYP3A4
1925
 no
CYP2B6
1001
 no
no (co-administration study)
Comment: diphenoxylate had no effect on buproprion AUC and Cmax
Page: 18805.0
CYP2D6
1891
 no
no (co-administration study)
Comment: diphenoxylate had no effect on metroprolol AUC and Cmax
Page: 18805.0
CYP3A4
1925
 no
no (co-administration study)
Comment: diphenoxylate had no effect on testosterone AUC and Cmax
Page: 18805.0
Ca2+ channels
60
 unlikely
CYP1A2
1692
 yes
yes (co-administration study)
Comment: diphenoxylate decreased phenacetin AUC and Cmax
Page: abstract
CYP2C9
1819
 yes
yes (co-administration study)
Comment: diphenoxylate decreased tolbutamide AUC and Cmax
Page: abstract
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
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
Treatment options for fecal incontinence.
2001 Jan
Antidiarrhoeal effects of methanolic root extract of Hemidesmus indicus (Indian sarsaparilla)--an in vitro and in vivo study.
2003 Apr
Protective effect of Arque-Ajeeb on acute experimental diarrhoea in rats.
2004 Jul 6
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
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
Toward achieving optimal response: understanding and managing antidepressant side effects.
2008
Are one or two dangerous? Diphenoxylate-atropine exposure in toddlers.
2008 Jan
[Methodological study on quality evaluation of rhubarb based on purgative bioassay].
2008 Jun
[Topic: Treating travelers' diarrhea. When should medication be given?].
2008 Jun
Antimotility agents for chronic diarrhoea in people with HIV/AIDS.
2008 Oct 8
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Patents

Patents

JP2009526755A
447

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 Dec 16 15:50:13 GMT 2023 , Edited by admin on Sat Dec 16 15:50:13 GMT 2023
NCI_THESAURUS C266
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WHO-ATC A07DA01
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LIVERTOX NBK548367
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WHO-VATC QA07DA01
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DEA NO. 9170
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Code System Code Type Description
PUBCHEM
13505
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PRIMARY
CAS
915-30-0
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PRIMARY
DRUG CENTRAL
918
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PRIMARY
NCI_THESAURUS
C62024
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PRIMARY
DRUG BANK
DB01081
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PRIMARY
MESH
D004157
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PRIMARY
LACTMED
Diphenoxylate
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PRIMARY
HSDB
3067
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PRIMARY
ChEMBL
CHEMBL1201294
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PRIMARY
DAILYMED
73312P173G
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PRIMARY
IUPHAR
7164
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PRIMARY
EPA CompTox
DTXSID8022951
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PRIMARY
INN
850
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PRIMARY
CHEBI
4639
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PRIMARY
SMS_ID
100000082328
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PRIMARY
MERCK INDEX
m4613
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PRIMARY Merck Index
FDA UNII
73312P173G
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PRIMARY
ECHA (EC/EINECS)
213-020-1
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PRIMARY
EVMPD
SUB07212MIG
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PRIMARY
RXCUI
3500
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PRIMARY RxNorm
WIKIPEDIA
DIPHENOXYLATE
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PRIMARY
ACTIVE MOIETY
Structure of DIPHENOXYLATE
METABOLITE (PARENT)
Structure of DIFENOXIN
SALT/SOLVATE (PARENT)
Structure of DIPHENOXYLATE HYDROCHLORIDE
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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