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

Details

Stereochemistry ACHIRAL
Molecular Formula C30H32N2O2
Molecular Weight 452.5873
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

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

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P35372|||G8XRH8|||Q5TDA1|||Q9UN57
Gene ID: 4988.0
Gene Symbol: OPRM1
Target Organism: Homo sapiens (Human)
Sources: ISBN-13: 978-0323055932
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
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
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
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
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
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
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%
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:
unhealthy
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:
unhealthy
Other AEs: Drug dependence...
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:
unhealthy
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor
yes (co-administration study)
Comment: diphenoxylate decreased omeprazole AUC and Cmax
Page: abstract
no
no
no
no
no (co-administration study)
Comment: diphenoxylate had no effect on buproprion AUC and Cmax
Page: 18805.0
no
no (co-administration study)
Comment: diphenoxylate had no effect on metroprolol AUC and Cmax
Page: 18805.0
no
no (co-administration study)
Comment: diphenoxylate had no effect on testosterone AUC and Cmax
Page: 18805.0
unlikely
yes
yes (co-administration study)
Comment: diphenoxylate decreased phenacetin AUC and Cmax
Page: abstract
yes
yes (co-administration study)
Comment: diphenoxylate decreased tolbutamide AUC and Cmax
Page: abstract
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
[Irritable colon].
2001 Aug 20
Irritable bowel syndrome: update on pathogenesis and management.
2002 Jan-Mar
The efficacy of octreotide in the therapy of acute radiation-induced diarrhea: a randomized controlled study.
2002 Sep 1
Drug treatment for faecal incontinence in adults.
2003
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
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
Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?
2005 May 10
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
Anticholinergic activity of 107 medications commonly used by older adults.
2008 Jul
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
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
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
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
Effect of an antidiabetic polysaccharide from Inula japonica on constipation in normal and two models of experimental constipated mice.
2010 Nov
Patents

Sample Use Guides

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 UTC 2023 , Edited by admin on Sat Dec 16 15:50:13 UTC 2023
NCI_THESAURUS C266
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WHO-ATC A07DA01
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LIVERTOX NBK548367
Created by admin on Sat Dec 16 15:50:13 UTC 2023 , Edited by admin on Sat Dec 16 15:50:13 UTC 2023
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
Created by admin on Sat Dec 16 15:50:13 UTC 2023 , Edited by admin on Sat Dec 16 15:50:13 UTC 2023
PRIMARY