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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

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
Therapeutic response to octreotide in patients with refractory CPT-11 induced diarrhea.
2001
Irritable bowel syndrome: update on pathogenesis and management.
2002 Jan-Mar
Drug treatment for faecal incontinence in adults.
2003
Small amounts of some drugs can be toxic to young children: one pill or one swallow can require aggressive treatment.
2003 Jun
Potential roles of P-gp and calcium channels in loperamide and diphenoxylate transport.
2003 Nov 15
The clinical and pathologic significance of microscopic colitis.
2004 May-Jun
[Treatment of 64 cases with compound diphenoxylate poisoning with naloxone].
2004 Sep
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
Pharmacotherapy for fecal incontinence: a review.
2007 May
Myasthenia gravis.
2007 Nov 6
Toward achieving optimal response: understanding and managing antidepressant side effects.
2008
Management of side effects associated with sunitinib therapy for patients with renal cell carcinoma.
2009 Feb 18
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
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
Antidiarrheal activity of extracts and compound from Trilepisium madagascariense stem bark.
2010 Jun
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 HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   VANDF   WHO-DD   WHO-IP  
Common Name English
COLONAID COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE CII
USP-RS  
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF LONOX
Common Name English
LOMOTIL COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF COLONAID
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 COMPONENT OF LOMOTIL
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF LO-TROL
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 COMPONENT OF LOMANATE
Common Name English
Diphenoxylate hydrochloride [WHO-DD]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF LOW-QUEL
Common Name English
4-PIPERIDINECARBOXYLIC ACID, 1-(3-CYANO-3,3-DIPHENYLPROPYL)-4-PHENYL-, ETHYL ESTER, MONOHYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF LOGEN
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [MART.]
Common Name English
DIPHENOXYLATE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
LOW-QUEL COMPONENT DIPHENOXYLATE HYDROCHLORIDE
Common Name English
DIPHENOXYLATE HYDROCHLORIDE COMPONENT OF DI-ATRO
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C266
Created by admin on Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C28995
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PRIMARY
EPA CompTox
DTXSID3047843
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PRIMARY
SMS_ID
100000089955
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PRIMARY
RS_ITEM_NUM
1219008
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PRIMARY
CAS
3810-80-8
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PRIMARY
PUBCHEM
19650
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PRIMARY
EVMPD
SUB01776MIG
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PRIMARY
ECHA (EC/EINECS)
223-287-6
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PRIMARY
CHEBI
59784
Created by admin on Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
DIPHENOXYLATE HYDROCHLORIDE
Created by admin on Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
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 Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
PRIMARY
MERCK INDEX
m4613
Created by admin on Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
PRIMARY Merck Index
DRUG BANK
DBSALT000809
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PRIMARY
RXCUI
82005
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PRIMARY RxNorm
DAILYMED
W24OD7YW48
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PRIMARY
FDA UNII
W24OD7YW48
Created by admin on Fri Dec 15 14:59:29 GMT 2023 , Edited by admin on Fri Dec 15 14:59:29 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of DIPHENOXYLATE
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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