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Details

Stereochemistry ACHIRAL
Molecular Formula C29H33ClN2O2
Molecular Weight 477.038
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOPERAMIDE

SMILES

CN(C)C(=O)C(CCN1CCC(O)(CC1)C2=CC=C(Cl)C=C2)(C3=CC=CC=C3)C4=CC=CC=C4

InChI

InChIKey=RDOIQAHITMMDAJ-UHFFFAOYSA-N
InChI=1S/C29H33ClN2O2/c1-31(2)27(33)29(24-9-5-3-6-10-24,25-11-7-4-8-12-25)19-22-32-20-17-28(34,18-21-32)23-13-15-26(30)16-14-23/h3-16,34H,17-22H2,1-2H3

HIDE SMILES / InChI

Molecular Formula C29H33ClN2O2
Molecular Weight 477.038
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Loperamide is a commonly used over-the-counter (OTC) and prescription medicine that is approved to help control symptoms of diarrhea, including Travelers’ Diarrhea. The maximum approved daily dose for adults is 8 mg per day for OTC use and 16 mg per day for prescription use. It is sold under the OTC brand name Imodium A-D, as store brands, and as generics. In vitro and animal studies show that IMODIUM® (loperamide hydrochloride) acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide binds to the opiate receptor in the gut wall. Consequently, it inhibits the release of acetylcholine and prostaglandins, thereby reducing propulsive peristalsis, and increasing intestinal transit time. Loperamide increases the tone of the anal sphincter, thereby reducing incontinence and urgency. Loperamide is also indicated for reducing the volume of discharge from ileostomies. In man, Loperamide prolongs the transit time of the intestinal contents. It reduces the daily fecal volume, increases the viscosity and bulk density, and diminishes the loss of fluid and electrolytes. Tolerance to the antidiarrheal effect has not been observed. Loperamide is an opioid receptor agonist and acts on the mu opioid receptors in the myenteric plexus large intestines; it does not affect the central nervous system like other opioids. It works specifically by decreasing the activity of the myenteric plexus which decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. Loperamide also decreases colonic mass movements and suppresses the gastrocolic reflex.

CNS Activity

Curator's Comment: Non-penetrant at recommended doses, although an opioid, at therapeutic doses it acts primarily on the gastrointestinal tissues; however, larger than recommended amounts facilitate central nervous system (CNS) penetration

Originator

Curator's Comment: Loperamide was first synthesized by Paul Janssen of Janssen Pharmaceutica in 1969

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IMODIUM A-D

Approved Use

Use controls symptoms of diarrhea, including Travelers'Diarrhea

Launch Date

1976
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.24 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOPERAMIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
26.1 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOPERAMIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.8 h
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOPERAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
11.2 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOPERAMIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
4 mg single, oral
dose: 4 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LOPERAMIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day multiple, oral
Overdose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 26
Disc. AE: Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Cardiac arrest (grade 5)
Sources:
792 mg 1 times / day multiple, oral
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources:
unhealthy, 28
Health Status: unhealthy
Age Group: 28
Sex: M
Sources:
Disc. AE: Syncope, Tachycardia...
AEs leading to
discontinuation/dose reduction:
Syncope
Tachycardia
Electrocardiogram QTc interval prolonged
Cardiac arrest
Sources:
400 mg 1 times / day multiple, oral
Overdose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 30
Disc. AE: Syncope, Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Syncope
Cardiac arrest
Torsades de pointes
Sources:
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Disc. AE: Torsades de pointes, Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Torsades de pointes
Cardiac arrest
Sources:
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Disc. AE: Ventricular tachycardia, Syncope...
AEs leading to
discontinuation/dose reduction:
Ventricular tachycardia
Syncope
Sources:
AEs

AEs

AESignificanceDosePopulation
Cardiac arrest grade 5
Disc. AE
400 mg 2 times / day multiple, oral
Overdose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy, 26
Cardiac arrest Disc. AE
792 mg 1 times / day multiple, oral
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources:
unhealthy, 28
Health Status: unhealthy
Age Group: 28
Sex: M
Sources:
Electrocardiogram QTc interval prolonged Disc. AE
792 mg 1 times / day multiple, oral
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources:
unhealthy, 28
Health Status: unhealthy
Age Group: 28
Sex: M
Sources:
Syncope Disc. AE
792 mg 1 times / day multiple, oral
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources:
unhealthy, 28
Health Status: unhealthy
Age Group: 28
Sex: M
Sources:
Tachycardia Disc. AE
792 mg 1 times / day multiple, oral
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources:
unhealthy, 28
Health Status: unhealthy
Age Group: 28
Sex: M
Sources:
Cardiac arrest Disc. AE
400 mg 1 times / day multiple, oral
Overdose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 30
Syncope Disc. AE
400 mg 1 times / day multiple, oral
Overdose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 30
Torsades de pointes Disc. AE
400 mg 1 times / day multiple, oral
Overdose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 30
Cardiac arrest Disc. AE
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Torsades de pointes Disc. AE
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Syncope Disc. AE
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Ventricular tachycardia Disc. AE
16 mg 8 times / day multiple, oral
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources:
unhealthy
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
strong [IC50 0.05 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
yes
yes
yes (co-administration study)
Comment: single 4-mg dose of loperamide hydrochloride was co-administered with 600 mg gemfibrozil, a strong inhibitor of CYP2C8, on day 3 of a 5-day treatment with gemfibrozil twice daily, the mean peak plasma concentration and the systemic exposure to loperamide was increased by 1.6-fold and 2.2-fold, respectively
Page: 2.0
yes
yes (co-administration study)
Comment: Concomitant administration of multiple doses of 100 mg itraconazole twice daily, an inhibitor of both CYP3A4, with a single 4-mg dose of loperamide hydrochloride increased the peak plasma concentration and the systemic exposure to loperamide by 2.9-fold and 3.8-fold, respectively
Page: 2.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers.
2003-06-18
Evaluation of different calorimetric methods to determine the glass transition temperature and molecular mobility below T(g) for amorphous drugs.
2003-06-18
[Malaria--case report].
2003-06-06
Facilitation of drug entry into the CNS via transient permeation of blood brain barrier: laboratory and preliminary clinical evidence from bradykinin receptor agonist, Cereport.
2003-05-15
I get occasional diarrhea. Is there anything nonprescription that's particularly effective for that?
2003-05
Loperamide mobilizes intracellular Ca2+ stores in insulin-secreting HIT-T15 cells.
2003-05
Postinfectious irritable bowel syndrome.
2003-05
Suspicion of microscopic colitis raised by sonographic examination.
2003-05
Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.
2003-04-22
[Ileus after the use of loperamide in a child with acute diarrhea].
2003-04-05
Dose-response relationship and mechanism of action of Saccharomyces boulardii in castor oil-induced diarrhea in rats.
2003-04
Effect of loperamide on gastro-oesophageal reflux.
2003-04
Pharmacologic therapy for the irritable bowel syndrome.
2003-04
Antidiarrhoeal activity of hot water extract of black tea (Camellia sinensis).
2003-04
Cost of illness in the 1993 waterborne Cryptosporidium outbreak, Milwaukee, Wisconsin.
2003-04
EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer.
2003-03-10
Morphine and d-amphetamine nullify each others' hypothermic effects in mice.
2003-02
Racecadotril versus loperamide: antidiarrheal research revisited.
2003-02
Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats.
2003-02
Travellers' diarrhoea.
2003-02
Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.
2003-01-30
Evaluation of anti-diarrhoeal activity in seed extracts of Mangifera indica.
2003-01
Acute gastroenteritis in children.
2002-12
Effects of full-thickness burns on nociceptor sensitization in anesthetized rats.
2002-12
Management of irritable bowel syndrome.
2002-11-15
Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer.
2002-11-04
Systematic review on the management of irritable bowel syndrome in North America.
2002-11
Evidence-based position statement on the management of irritable bowel syndrome in North America.
2002-11
Lymphocytic colitis: clinical features, treatment, and outcomes.
2002-11
Spreading depression: imaging and blockade in the rat neocortical brain slice.
2002-11
Antipruritic and antihyperalgesic actions of loperamide and analogs.
2002-10-25
Irinotecan, cisplatin and mitomycin in inoperable gastro-oesophageal and pancreatic cancers - a new active regimen.
2002-10-07
New developments in the diagnosis and treatment of irritable bowel syndrome.
2002-10
[Taking charge of adult's anal incontinence].
2002-09
[Travellers' acute diarrhea].
2002-09
Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth.
2002-09
Functional effects of systemically administered agonists and antagonists of mu, delta, and kappa opioid receptor subtypes on body temperature in mice.
2002-09
A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer.
2002-08-12
[Effect of jianpi wenshen decoction on serum gastrin, plasma motilin and somatostatin in patients of diabetic diarrhea].
2002-08
Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of activity in a phase II trial.
2002-08
Irritable bowel syndrome: update on pathogenesis and management.
2002-07-16
Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds.
2002-07
Fumagillin treatment of intestinal microsporidiosis.
2002-06-20
Acute gastroenteritis in children.
2002-06
A multinational comparison of racecadotril and loperamide in the treatment of acute watery diarrhoea in adults.
2002-06
Laxative and anti-diarrheal activity of polycarbophil in mice and rats.
2002-06
Determination of the active ingredient loperamide hydrochloride in pharmaceutical caplets by high performance thin layer chromatography with ultraviolet absorption densitometry of fluorescence quenched zones.
2002-05-25
Short bowel syndrome: a nutritional and medical approach.
2002-05-14
Intestinal cryptosporidiosis as an initial manifestation in a previously healthy Japanese patient with AIDS.
2002
Recent concepts in fecal incontinence.
2001-08
Patents

Patents

Sample Use Guides

Usual Adult Dose for Diarrhea - Acute Tablets, capsules, and liquid: Initial: 4 mg orally after the first loose stool, then Maintenance: 2 mg after each loose stool, not to exceed 16 mg in any 24-hour period. Clinical improvement is usually observed within 48 hours. Chewable tablets: Initial: 4 mg after the first loose stool, then Maintenance: 2 mg after each subsequent loose stool, but not exceeding 8 mg in 24 hours. Usual Adult Dose for Diarrhea - Chronic Tablets, capsules, and liquid: Initial: 4 mg orally once followed by 2 mg orally after each loose stool, not to exceed 16 mg in any 24-hour period. Maintenance: The average daily maintenance dosage is 4 to 8 mg. Clinical improvement is usually observed within 10 days. If clinical improvement is not observed at a maximum dosage of 16 mg for duration of 10 days, symptoms are unlikely to be controlled by further administration.
Route of Administration: Oral
Loperamide caused a concentration-dependent inhibition of the ascending contractile reflex response in the rat ileum with an IC(50) of 1.4x10(-7)M
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:06:15 GMT 2025
Edited
by admin
on Mon Mar 31 18:06:15 GMT 2025
Record UNII
6X9OC3H4II
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOPERAMIDE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
4-(P-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-1-PIPERIDINEBUTYRAMIDE
Preferred Name English
LOPERAMIDE [VANDF]
Common Name English
1-PIPERIDINEBUTANAMIDE, 4-(4-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-
Systematic Name English
Loperamide [WHO-DD]
Common Name English
loperamide [INN]
Common Name English
LOPERAMIDE [MI]
Common Name English
LOPERAMIDE [JAN]
Common Name English
LOPERAMIDE OXIDE MONOHYDRATE IMPURITY A [EP IMPURITY]
Common Name English
Classification Tree Code System Code
WHO-VATC QA07DA03
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
WHO-ATC A07DA53
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
WHO-ATC A07DA03
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
NCI_THESAURUS C1506
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
NDF-RT N0000175690
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
NCI_THESAURUS C266
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
NDF-RT N0000000174
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
LIVERTOX NBK547935
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
WHO-VATC QA07DA53
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
Code System Code Type Description
FDA UNII
6X9OC3H4II
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
CAS
53179-11-6
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
INN
3098
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID6045165
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
ChEMBL
CHEMBL841
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
PUBCHEM
3955
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
MESH
D008139
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
WIKIPEDIA
LOPERAMIDE
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
HSDB
8344
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
NCI_THESAURUS
C618
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
LACTMED
Loperamide
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
EVMPD
SUB08572MIG
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
SMS_ID
100000082007
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
IUPHAR
7215
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
CHEBI
6532
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
DRUG CENTRAL
1599
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
DRUG BANK
DB00836
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
RXCUI
6468
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY RxNorm
MERCK INDEX
m6898
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY Merck Index
ECHA (EC/EINECS)
258-416-5
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
DAILYMED
6X9OC3H4II
Created by admin on Mon Mar 31 18:06:16 GMT 2025 , Edited by admin on Mon Mar 31 18:06:16 GMT 2025
PRIMARY
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