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Details

Stereochemistry ACHIRAL
Molecular Formula C29H33ClN2O2.ClH
Molecular Weight 513.4994
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LOPERAMIDE HYDROCHLORIDE

SMILES

CN(C)C(=O)C(CCN1CCC(CC1)(c2ccc(cc2)Cl)O)(c3ccccc3)c4ccccc4.Cl

InChI

InChIKey=PGYPOBZJRVSMDS-UHFFFAOYSA-N
InChI=1S/C29H33ClN2O2.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C29H33ClN2O2
Molecular Weight 477.0385
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

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
Herbal medicines as a factor in delirium.
1999 Jul
Recent concepts in fecal incontinence.
2001 Aug
Effects of loperamide and other opioid-related substances on the transcriptional regulation of the rat pro-opiomelanocortin gene in AtT20 cells.
2001 Aug
Drug transporters revisited.
2001 Feb
Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial.
2001 Jan
Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance.
2001 Jul
Control of irinotecan-induced diarrhea by octreotide after loperamide failure.
2001 Jun
Nanoparticulate systems for brain delivery of drugs.
2001 Mar 23
Traveler's diarrhea.
2001 Sep
Irinotecan in relapsed or refractory non-Hodgkin's lymphomas. Indications of activity in a phase II trial.
2002 Aug
Acute gastroenteritis in children.
2002 Dec
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 Jan-Feb
Systematic review on the management of irritable bowel syndrome in North America.
2002 Nov
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
Racecadotril versus loperamide: antidiarrheal research revisited.
2003 Feb
Drug complexation, in vitro release and cellular entry of dendrimers and hyperbranched polymers.
2003 Jun 18
Evaluation of different calorimetric methods to determine the glass transition temperature and molecular mobility below T(g) for amorphous drugs.
2003 Jun 18
[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
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 Fri Jun 25 21:03:39 UTC 2021
Edited
by admin
on Fri Jun 25 21:03:39 UTC 2021
Record UNII
77TI35393C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LOPERAMIDE HYDROCHLORIDE
EP   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
USAN  
Official Name English
LOPERAMIDE HYDROCHLORIDE [USP-RS]
Common Name English
LOPERAMIDE HYDROCHLORIDE COMPONENT OF IMODIUM MULTI-SYMPTOM RELIEF
Common Name English
R 18,553
Code English
LOPERAMIDE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
LOPERAMIDE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
1-PIPERIDINEBUTANAMIDE, 4-(4-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-, MONOHYDROCHLORIDE
Common Name English
LOPERAMIDE HYDROCHLORIDE [MI]
Common Name English
LOPERAMIDE HYDROCHLORIDE [WHO-DD]
Common Name English
LOPERAMIDE HYDROCHLORIDE [EP]
Common Name English
LOPERAMIDE HYDROCHLORIDE [VANDF]
Common Name English
LOPERAMIDI HYDROCHLORIDUM [WHO-IP LATIN]
Common Name English
R-18553
Code English
LOPERAMIDE HYDROCHLORIDE [MART.]
Common Name English
LOPERAMIDE HYDROCHLORIDE [WHO-IP]
Common Name English
LOPERAMIDE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
LOPERAMIDE HCL
Common Name English
NSC-696356
Code English
LOPERAMIDE HYDROCHLORIDE [USAN]
Common Name English
4-(P-CHLOROPHENYL)-4-HYDROXY-N,N-DIMETHYL-.ALPHA.,.ALPHA.-DIPHENYL-1-PIPERIDINEBUTYRAMIDE MONOHYDROCHLORIDE
Common Name English
LOPERAMIDE HYDROCHLORIDE [JAN]
Common Name English
IMODIUM
Brand Name English
IMODIUM MULTI-SYMPTOM RELIEF COMPONENT LOPERAMIDE HYDROCHLORIDE
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C266
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
Code System Code Type Description
USP_CATALOG
1370000
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY USP-RS
DRUG BANK
DBSALT000709
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
EVMPD
SUB02969MIG
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
LOPERAMIDE HYDROCHLORIDE
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY Description: A white to slightly yellowish powder. Solubility: Slightly soluble in water and in dilute acids; freely soluble in methanol R. Category: Antidiarrhoeal drug. Storage: Loperamide hydrochloride should be kept in a well-closed container. Definition: Loperamide hydrochloride contains not less than 98.0% and not more than 102.0% of C29H33ClN2O2,HCl, calculated with reference to the dried substance.
PUBCHEM
71420
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
FDA UNII
77TI35393C
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
MERCK INDEX
M6898
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY Merck Index
RXCUI
82038
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY RxNorm
CAS
34552-83-5
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
NCI_THESAURUS
C1584
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
ChEMBL
CHEMBL841
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
ECHA (EC/EINECS)
252-082-4
Created by admin on Fri Jun 25 21:03:40 UTC 2021 , Edited by admin on Fri Jun 25 21:03:40 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.7
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.3
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY