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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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

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

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
0.53 nM [Ki]
156.0 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
IMODIUM A-D

Cmax

ValueDoseCo-administeredAnalytePopulation
2.24 ng/mL
8 mg single, oral
LOPERAMIDE blood
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
26.1 ng × h/mL
8 mg single, oral
LOPERAMIDE blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
11.2 h
8 mg single, oral
LOPERAMIDE blood
Homo sapiens
10.8 h
4 mg single, oral
LOPERAMIDE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
4 mg single, oral
LOPERAMIDE plasma
Homo sapiens

Doses

AEs

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
Record UNII
6X9OC3H4II
Record Status Validated (UNII)
Record Version