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Details

Stereochemistry ACHIRAL
Molecular Formula C30H32N2O2.ClH
Molecular Weight 489.048
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DIPHENOXYLATE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=SHTAFWKOISOCBI-UHFFFAOYSA-N
InChI=1S/C30H32N2O2.ClH/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;1H

HIDE SMILES / InChI
Molecular Formula C30H32N2O2
Molecular Weight 452.5873
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
4002
Curator's Comment: At high doses it exhibits codeine-like subjective effects.

Originator

Approval Year

1960
105
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
2752
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8583
LOMOTIL

Approved Use

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

Launch Date

1960
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
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
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
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
1087

inhibitor
2252
inducer
440
inducer
109

inhibitor
2507
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
Ca2+ channels
59

CYP2B6
926
P-gp
2052
CYP2C19
329

CYP1A2
832

CYP2B6
669
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C19
2141
 minor
yes (co-administration study)
Comment: diphenoxylate decreased omeprazole AUC and Cmax
Page: abstract
CYP2B6
1160
 no
CYP2D6
2546
 no
CYP3A4
2633
 no
CYP2B6
1160
 no
no (co-administration study)
Comment: diphenoxylate had no effect on buproprion AUC and Cmax
Page: 18805.0
CYP2D6
2546
 no
no (co-administration study)
Comment: diphenoxylate had no effect on metroprolol AUC and Cmax
Page: 18805.0
CYP3A4
2633
 no
no (co-administration study)
Comment: diphenoxylate had no effect on testosterone AUC and Cmax
Page: 18805.0
Ca2+ channels
62
 unlikely
CYP1A2
2333
 yes
yes (co-administration study)
Comment: diphenoxylate decreased phenacetin AUC and Cmax
Page: abstract
CYP2C9
2497
 yes
yes (co-administration study)
Comment: diphenoxylate decreased tolbutamide AUC and Cmax
Page: abstract
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
2052
 no
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
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
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
Management of acute cancer treatment-induced diarrhea.
2003 Nov
Potential roles of P-gp and calcium channels in loperamide and diphenoxylate transport.
2003 Nov 15
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
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
Loperamide therapy for acute diarrhea in children: systematic review and meta-analysis.
2007 Mar 27
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
[Methodological study on quality evaluation of rhubarb based on purgative bioassay].
2008 Jun
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
475

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
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:34:16 GMT 2025
Edited
by admin
on Mon Mar 31 17:34:16 GMT 2025
Record UNII
W24OD7YW48
Record Status Validated (UNII)
Record Version
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Name Type Language
COLONAID COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Preferred Name English
DIPHENOXYLATE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   VANDF   WHO-DD   WHO-IP  
Common Name English
DIPHENOXYLATE HYDROCHLORIDE CII
USP-RS  
Common Name English
LOMOTIL COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
LOGEN COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [MI]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
R-1132 (ANTIPERISTALTIC)
Code English
LONOX COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [VANDF]
Common Name English
LO-TROL COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [USP-RS]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [WHO-IP]
Common Name English
DIPHENOXYLATE HCL
Common Name English
DI-ATRO COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
LOMANATE COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
ETHYL 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYLISONIPECOTATE MONOHYDROCHLORIDE
Systematic Name English
ISONIPECOTIC ACID, 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYL-, ETHYL ESTER, MONOHYDROCHLORIDE
Systematic Name English
Diphenoxylate hydrochloride [WHO-DD]
Common Name English
4-PIPERIDINECARBOXYLIC ACID, 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYL-, ETHYL ESTER, MONOHYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [MART.]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
LOW-QUEL COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C266
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
Code System Code Type Description
NCI_THESAURUS
C28995
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID3047843
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
SMS_ID
100000089955
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
RS_ITEM_NUM
1219008
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
CAS
3810-80-8
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
PUBCHEM
19650
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
EVMPD
SUB01776MIG
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
ECHA (EC/EINECS)
223-287-6
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
CHEBI
59784
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
DIPHENOXYLATE HYDROCHLORIDE
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY Description:A white or almost white, crystalline powder; odourless.Solubility: Sparingly soluble in water, acetone R and ethanol (~750 g/l) TS; practically insoluble in ether R.Category: Antidiarrhoeal drug.Storage: Diphenoxylate hydrochloride should be kept in a well-closed container.Requirements:Definition: Diphenoxylate hydrochloride contains not less than 98.0% and not more than 101.0% of C30H32N2O2,HCl, calculated with reference to the dried substance.
ChEMBL
CHEMBL1201294
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
MERCK INDEX
m4613
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY Merck Index
DRUG BANK
DBSALT000809
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
RXCUI
82005
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY RxNorm
DAILYMED
W24OD7YW48
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
FDA UNII
W24OD7YW48
Created by admin on Mon Mar 31 17:34:16 GMT 2025 , Edited by admin on Mon Mar 31 17:34:16 GMT 2025
PRIMARY
Related Record Type Details
Structure of DIPHENOXYLATE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of DIFENOXIN
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
Structure of DIPHENOXYLATE
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