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Details

Stereochemistry ACHIRAL
Molecular Formula C29H33ClN2O2
Molecular Weight 477.0385
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(CC1)(c2ccc(cc2)Cl)O)(c3ccccc3)c4ccccc4

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
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

2.20579201E11
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
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
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
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 26
Sex: M
Population Size: 1
Sources:
Disc. AE: Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Cardiac arrest (grade 5)
Sources:
792 mg 1 times / day multiple, oral (total daily dose)
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources: Page: p.954
unhealthy, 28
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.954
Disc. AE: Syncope, Tachycardia...
AEs leading to
discontinuation/dose reduction:
Syncope
Tachycardia
Electrocardiogram QTc interval prolonged
Cardiac arrest
Sources: Page: p.954
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 30
Sex: M
Population Size: 1
Sources:
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 (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.1, 3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.1, 3
Disc. AE: Torsades de pointes, Cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Torsades de pointes
Cardiac arrest
Sources: Page: p.1, 3
16 mg 8 times / day multiple, oral (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.3
Disc. AE: Ventricular tachycardia, Syncope...
AEs leading to
discontinuation/dose reduction:
Ventricular tachycardia
Syncope
Sources: Page: p.3
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 26
Sex: M
Population Size: 1
Sources:
Cardiac arrest Disc. AE
792 mg 1 times / day multiple, oral (total daily dose)
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources: Page: p.954
unhealthy, 28
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.954
Electrocardiogram QTc interval prolonged Disc. AE
792 mg 1 times / day multiple, oral (total daily dose)
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources: Page: p.954
unhealthy, 28
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.954
Syncope Disc. AE
792 mg 1 times / day multiple, oral (total daily dose)
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources: Page: p.954
unhealthy, 28
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.954
Tachycardia Disc. AE
792 mg 1 times / day multiple, oral (total daily dose)
Overdose
Dose: 792 mg, 1 times / day
Route: oral
Route: multiple
Dose: 792 mg, 1 times / day
Sources: Page: p.954
unhealthy, 28
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 28
Sex: M
Population Size: 1
Sources: Page: p.954
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 30
Sex: M
Population Size: 1
Sources:
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 30
Sex: M
Population Size: 1
Sources:
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
n = 1
Health Status: unhealthy
Condition: Opiate abuse
Age Group: 30
Sex: M
Population Size: 1
Sources:
Cardiac arrest Disc. AE
16 mg 8 times / day multiple, oral (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.1, 3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.1, 3
Torsades de pointes Disc. AE
16 mg 8 times / day multiple, oral (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.1, 3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.1, 3
Syncope Disc. AE
16 mg 8 times / day multiple, oral (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.3
Ventricular tachycardia Disc. AE
16 mg 8 times / day multiple, oral (total daily dose)
Recommended
Dose: 16 mg, 8 times / day
Route: oral
Route: multiple
Dose: 16 mg, 8 times / day
Sources: Page: p.3
unhealthy
Health Status: unhealthy
Condition: Diarrhea
Sources: Page: p.3
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
Recent concepts in fecal incontinence.
2001 Aug
Effects of yogurt supplemented with brewer's yeast cell wall on constipation and intestinal microflora in rats.
2001 Dec
Tropical diarrhoea: new developments in traveller's diarrhoea.
2001 Oct
[Colonic microflora and motility. Physiological data and during irritable bowel syndrome].
2001 Sep
Intestinal cryptosporidiosis as an initial manifestation in a previously healthy Japanese patient with AIDS.
2002
Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein.
2002 Apr
Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of collies from the northwestern United States.
2002 Apr
[Effect of jianpi wenshen decoction on serum gastrin, plasma motilin and somatostatin in patients of diabetic diarrhea].
2002 Aug
Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of activity in a phase II trial.
2002 Aug
A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer.
2002 Aug 12
Acute gastroenteritis in children.
2002 Dec
Effects of full-thickness burns on nociceptor sensitization in anesthetized rats.
2002 Dec
K+ channel cAMP activated in guinea pig gallbladder epithelial cells.
2002 Feb 8
Irritable bowel syndrome: update on pathogenesis and management.
2002 Jan-Mar
Irritable bowel syndrome neuropharmacology. A review of approved and investigational compounds.
2002 Jul
Acute gastroenteritis in children.
2002 Jun
A multinational comparison of racecadotril and loperamide in the treatment of acute watery diarrhoea in adults.
2002 Jun
Laxative and anti-diarrheal activity of polycarbophil in mice and rats.
2002 Jun
Fumagillin treatment of intestinal microsporidiosis.
2002 Jun 20
Fecal incontinence in anorectal malformations, neuropathy, and miscellaneous conditions.
2002 May
Short bowel syndrome: a nutritional and medical approach.
2002 May 14
Systematic review on the management of irritable bowel syndrome in North America.
2002 Nov
Evidence-based position statement on the management of irritable bowel syndrome in North America.
2002 Nov
Lymphocytic colitis: clinical features, treatment, and outcomes.
2002 Nov
Spreading depression: imaging and blockade in the rat neocortical brain slice.
2002 Nov
Management of irritable bowel syndrome.
2002 Nov 15
Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer.
2002 Nov 4
Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.
2002 Nov-Dec
New developments in the diagnosis and treatment of irritable bowel syndrome.
2002 Oct
Antipruritic and antihyperalgesic actions of loperamide and analogs.
2002 Oct 25
Irinotecan, cisplatin and mitomycin in inoperable gastro-oesophageal and pancreatic cancers - a new active regimen.
2002 Oct 7
[Taking charge of adult's anal incontinence].
2002 Sep
[Travellers' acute diarrhea].
2002 Sep
Antidiarrhoeal activity of seed extract of Albizzia lebbeck Benth.
2002 Sep
Functional effects of systemically administered agonists and antagonists of mu, delta, and kappa opioid receptor subtypes on body temperature in mice.
2002 Sep
Pharmacologic therapy for the irritable bowel syndrome.
2003 Apr
Antidiarrhoeal activity of hot water extract of black tea (Camellia sinensis).
2003 Apr
Cost of illness in the 1993 waterborne Cryptosporidium outbreak, Milwaukee, Wisconsin.
2003 Apr
Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.
2003 Apr 22
Morphine and d-amphetamine nullify each others' hypothermic effects in mice.
2003 Feb
Racecadotril versus loperamide: antidiarrheal research revisited.
2003 Feb
Lack of opioid or dopaminergic effects on unconditioned sexual incentive motivation in male rats.
2003 Feb
Travellers' diarrhoea.
2003 Feb
Evaluation of anti-diarrhoeal activity in seed extracts of Mangifera indica.
2003 Jan
[Malaria--case report].
2003 Jun 6
EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer.
2003 Mar 10
I get occasional diarrhea. Is there anything nonprescription that's particularly effective for that?
2003 May
Loperamide mobilizes intracellular Ca2+ stores in insulin-secreting HIT-T15 cells.
2003 May
Suspicion of microscopic colitis raised by sonographic examination.
2003 May
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 May 15
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
Name Type Language
LOPERAMIDE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
LOPERAMIDE [VANDF]
Common Name English
1-PIPERIDINEBUTANAMIDE, 4-(4-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-
Systematic Name English
4-(P-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-1-PIPERIDINEBUTYRAMIDE
Common Name English
LOPERAMIDE [INN]
Common Name English
LOPERAMIDE [WHO-DD]
Common Name English
LOPERAMIDE OXIDE MONOHYDRATE IMPURITY A [EP]
Common Name English
LOPERAMIDE [MI]
Common Name English
LOPERAMIDE [JAN]
Common Name English
Classification Tree Code System Code
WHO-VATC QA07DA03
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
WHO-ATC A07DA53
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
WHO-ATC A07DA03
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
NCI_THESAURUS C1506
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
NDF-RT N0000175690
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
NCI_THESAURUS C266
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
NDF-RT N0000000174
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
LIVERTOX 567
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
WHO-VATC QA07DA53
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
Code System Code Type Description
FDA UNII
6X9OC3H4II
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
CAS
53179-11-6
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
INN
3098
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
EPA CompTox
53179-11-6
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
ChEMBL
CHEMBL841
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
PUBCHEM
3955
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
MESH
D008139
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
WIKIPEDIA
LOPERAMIDE
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
HSDB
8344
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
NCI_THESAURUS
C618
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
LACTMED
Loperamide
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
EVMPD
SUB08572MIG
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
IUPHAR
7215
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
DRUG CENTRAL
1599
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
DRUG BANK
DB00836
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY
RXCUI
6468
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M6898
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
258-416-5
Created by admin on Sat Jun 26 04:21:16 UTC 2021 , Edited by admin on Sat Jun 26 04:21:16 UTC 2021
PRIMARY