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References

Trials

Economics

Properties

Spectra

Taxonomy

Loperamide

Targets (7)Enzymes (4)Transporters (1)Biointeractions (12)

Identification

Name

Loperamide

Accession Number

DB00836 (APRD00275)

Type

Small Molecule

Groups

Approved

Description

One of the long-acting synthetic antidiarrheals; it is not significantly absorbed from the gut, and has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally.

Structure

Similar Structures

Synonyms

Loperamid
Loperamida
Lopéramide
Loperamide
Loperamidum

External IDs

PJ 185 / R 18553

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Loperamide hydrochloride	77TI35393C	34552-83-5	PGYPOBZJRVSMDS-UHFFFAOYSA-N

Product Images

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Imodium	Capsule	2 mg/1	Oral	McNeil Consumer Healthcare	2008-02-26	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	Mc Kesson Contract Packaging	1991-09-18	2017-09-30
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	REMEDYREPACK INC.	2016-12-19	Not applicable
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	PD-Rx Pharmaceuticals, Inc.	1991-09-18	Not applicable
Loperamide hydrochloride	Capsule	2 mg/1	Oral	Northwind Pharmaceuticals	2014-10-22	Not applicable
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	Cardinal Health	1991-09-18	2012-10-31
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	Contract Pharmacy Services Pa	2017-09-20	Not applicable
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	Ncs Health Care Of Ky, Inc Dba Vangard Labs	2012-10-12	Not applicable
Loperamide Hydrochloride	Solution	2 mg/10mL	Oral	Cardinal Health	1992-04-30	2011-04-30
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	REMEDYREPACK INC.	2017-03-13	Not applicable
Loperamide Hydrochloride	Capsule	2 mg/1	Oral	Nucare Pharmaceuticals, Inc.	1993-05-01	Not applicable

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
7 Select Anti Diarrheal	Solution	1 mg/7.5mL	Oral	7-Eleven	2018-08-07	Not applicable
7 Select Anti Diarrheal	Tablet, film coated	2 mg/1	Oral	7 Eleven	2014-08-05	Not applicable
A D	Tablet, film coated	2 mg/1	Oral	Western Family Foods	2003-02-25	2017-08-29
A D	Tablet, film coated	2 mg/1	Oral	Western Family Foods	2003-04-10	2017-08-12
Alti-loperamide - 2mg Caplet	Tablet	2 mg	Oral	Altimed Pharma Inc.	1995-12-31	1997-08-14
Anti Diarrheal	Solution	1 mg/5mL	Oral	Rebel Distributors	1992-07-13	Not applicable
Anti Diarrheal	Capsule	2 mg/1	Oral	Nash Finch	2005-05-03	2018-04-02
Anti Diarrheal	Tablet	2 mg/1	Oral	Bedrock Brands, Llc	2005-05-03	2019-07-08
Anti Diarrheal	Capsule	2 mg/1	Oral	Walmart Stores	2005-05-03	2014-12-15
Anti Diarrheal	Tablet, film coated	2 mg/1	Oral	Remedy Repack	2016-05-19	2018-06-05

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Anti Diarrheal and Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	Walgreen Company	2018-10-10	Not applicable
Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	Amerisource Bergen	2018-12-28	Not applicable
Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	H E B	2018-11-15	Not applicable
Anti Diarrheal Plus Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	Meijer Distribution Inc	2018-10-16	Not applicable
Basic Care Loperamide Hydrochloride and Simethicone	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	L. Perrigo Company	2018-10-17	Not applicable
Dg Health Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	DOLGENCORP, LLC	2018-10-09	Not applicable
Doc in the Box All Day Supply	Loperamide hydrochloride (2 mg/1) + Acetaminophen (325 mg/1) + Acetaminophen (500 mg/1) + Calcium Carbonate (420 mg/1) + Dextromethorphan hydrobromide monohydrate (15 mg/1) + Guaifenesin (200 mg/1) + Ibuprofen (200 mg/1) + Phenylephrine hydrochloride (5 mg/1)	Kit	Oral	Doc In The Box Llc	2018-05-14	Not applicable
Equate Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	WAL-MART STORES INC	2018-12-30	Not applicable
Good Sense Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	L Perrigo Company	2018-10-11	Not applicable
Health Mart Anti Diarrheal Anti Gas	Loperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)	Tablet	Oral	McKesson	2018-10-10	Not applicable

International/Other Brands

Dimor (Nordic Drugs) / Fortasec (Esteve) / Imodium (Johnson & Johnson) / Kaopectate II (Chattem, Inc.) / Lopedium (Sandoz) / Lopedium express (Sandoz) / Lopex (Orion) / Maalox Anti-Diarrheal (Novartis International AG) / Pepto Diarrhea Control (Procter & Gamble )

Categories

UNII

6X9OC3H4II

CAS number

53179-11-6

Weight

Average: 477.038
Monoisotopic: 476.223056017

Chemical Formula

C₂₉H₃₃ClN₂O₂

InChI Key

RDOIQAHITMMDAJ-UHFFFAOYSA-N

InChI

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

IUPAC Name

4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-N,N-dimethyl-2,2-diphenylbutanamide

SMILES

CN(C)C(=O)C(CCN1CCC(O)(CC1)C1=CC=C(Cl)C=C1)(C1=CC=CC=C1)C1=CC=CC=C1

Pharmacology

Indication

For the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease or gastroenteritis. Also used for reducing the volume of discharge from ileostomies.

Associated Conditions

Pharmacodynamics

Loperamide is a synthetic anti-diarrheal indicated for the control and symptomatic relief of acute nonspecific diarrhea and of chronic diarrhea associated with inflammatory bowel disease. 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.

Mechanism of action

In vitro and animal studies show that Loperamide acts by slowing intestinal motility and by affecting water and electrolyte movement through the bowel. Loperamide inhibits peristaltic activity by a direct effect on the circular and longitudinal muscles of the intestinal wall. It is a non-selective calcium channel blocker and binds to opioid mu-receptors. Evidence also suggests that at higher concentrations it binds to calmodulin.

Target	Actions	Organism
AMu-type opioid receptor	agonist	Humans
ADelta-type opioid receptor	agonist	Humans
AKappa-type opioid receptor	agonist	Humans
UVoltage-dependent P/Q-type calcium channel subunit alpha-1A	inhibitor	Humans
UPro-opiomelanocortin	modulator	Humans
UCalmodulin	inhibitor	Humans
UNuclear receptor subfamily 1 group I member 3	Not Available	Humans

Absorption

Not significantly absorbed from the gut

Volume of distribution

Not Available

Protein binding

97%

Metabolism

Hepatic

Loperamide
N-Desmethyloperamide

Route of elimination

Excretion of the unchanged loperamide and its metabolites mainly occurs through the feces.

Half life

9.1 to 14.4 hours (average 10.8 hours)

Clearance

Not Available

Toxicity

Oral, mouse: LD₅₀ = 105 mg/kg. Symptoms of overdose include constipation, drowsiness, lethargy, and nausea.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	The metabolism of (R)-warfarin can be decreased when combined with Loperamide.
(S)-Warfarin	The metabolism of (S)-Warfarin can be decreased when combined with Loperamide.
2,4-thiazolidinedione	The risk or severity of hypoglycemia can be increased when Loperamide is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acid	The metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Loperamide.
4-hydroxycoumarin	The metabolism of 4-hydroxycoumarin can be decreased when combined with Loperamide.
4-Methoxyamphetamine	The metabolism of 4-Methoxyamphetamine can be decreased when combined with Loperamide.
5-androstenedione	The metabolism of 5-androstenedione can be decreased when combined with Loperamide.
6-Deoxyerythronolide B	The metabolism of Loperamide can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanine	The metabolism of 6-O-benzylguanine can be decreased when combined with Loperamide.
7-ethyl-10-hydroxycamptothecin	The metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Loperamide.

Food Interactions

Take without regard to meals. Increase liquid intake.

References

Synthesis Reference

Tsutomu Awamura, Hisanobu Nishikawa, Toshio Inagi, "FILM PREPARATION CONTAINING LOPERAMIDE HYDROCHLORIDE." U.S. Patent US20110159058, issued June 30, 2011.

US20110159058

General References

Not Available

External Links

Human Metabolome Database: HMDB0004999
KEGG Drug: D08144
KEGG Compound: C07080
PubChem Compound: 3955
PubChem Substance: 46504591
ChemSpider: 3818
BindingDB: 50017698
ChEBI: 6532
ChEMBL: CHEMBL841
Therapeutic Targets Database: DAP000425
PharmGKB: PA450262
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
PDRhealth: PDRhealth Drug Page
Wikipedia: Loperamide

ATC Codes

A07DA53 — Loperamide, combinations

A07DA03 — Loperamide

AHFS Codes

56:08.00 — Antidiarrhea Agents

FDA label

Download (55.5 KB)

MSDS

Download (73.8 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
0	Completed	Treatment	Pain NOS	1
1	Completed	Basic Science	Drug Drug Interaction (DDI)	1
1	Completed	Basic Science	Healthy Volunteers	1
1	Completed	Basic Science	Intestinal Obstruction	2
1	Completed	Treatment	Healthy Volunteers	2
1	Recruiting	Treatment	Neoplasms, Breast	1
2	Completed	Treatment	Cancer, Breast / Early-Stage Breast Carcinoma / Hormone Receptor Positive Tumor	1
2	Recruiting	Supportive Care	Metastatic Colorectal Cancers	1
2	Recruiting	Treatment	Early Stage HER2+ Breast Cancer	1
2	Recruiting	Treatment	Her2-Positive Breast Cancer	1
2	Withdrawn	Treatment	Malignancies	1
2, 3	Completed	Treatment	Diarrhoea Predominant Irritable Bowel Syndrome / Functional Diarrhea	1
2, 3	Completed	Treatment	Female Genital Diseases	1
2, 3	Completed	Treatment	Incontinence, Fecal	1
2, 3	Not Yet Recruiting	Treatment	Clostridium Difficile Infection (CDI)	1
3	Completed	Supportive Care	Colorectal Cancers / Severe or persistent diarrhea	1
3	Completed	Treatment	Incontinence, Fecal	1
3	Completed	Treatment	Lung Cancer Non-Small Cell Cancer (NSCLC)	1
3	Completed	Treatment	Severe or persistent diarrhea	1
3	Terminated	Prevention	Dehydration, Diverting Ileostomy, Loperamide	1
3	Terminated	Prevention	Severe or persistent diarrhea	1
3	Terminated	Treatment	Enteritis / Malignancies / Severe or persistent diarrhea	1
3	Terminated	Treatment	High Output Stoma	1
3	Terminated	Treatment	Rectal Carcinoma / Short Bowel Syndrome (SBS) / Ulcerative Colitis (UC)	1
4	Completed	Treatment	Travelers' Diarrhea	1
4	Completed	Treatment	Severe or persistent diarrhea	3
4	Recruiting	Treatment	Opiate withdrawal symptoms	1
4	Suspended	Treatment	Antibiotic Associated Diarrhea / Antibiotic-Associated Diarrhea / Clostridium Difficile	1
4	Terminated	Treatment	Relapsing Remitting Multiple Sclerosis (RRMS)	1
4	Withdrawn	Treatment	Incontinence, Fecal	1
Not Available	Completed	Not Available	Healthy Volunteers	1
Not Available	Completed	Treatment	Incontinence, Fecal	1
Not Available	Not Yet Recruiting	Basic Science	Intestinal Transit	1
Not Available	Recruiting	Treatment	Incontinence, Fecal	1
Not Available	Terminated	Treatment	Incontinence, Fecal	1

Pharmacoeconomics

Manufacturers

Mcneil consumer healthcare
Mcneil pediatrics
Janssen pharmaceutica products lp

Packagers

Advanced Pharmaceutical Services Inc.
AQ Pharmaceuticals Inc.
A-S Medication Solutions LLC
Cardinal Health
Chain Drug
Chattem Chemicals Inc.
Comprehensive Consultant Services Inc.
CVS Pharmacy
Dept Health Central Pharmacy
DHHS Program Support Center Supply Service Center
Direct Dispensing Inc.
Dispensing Solutions
Diversified Healthcare Services Inc.
Heartland Repack Services LLC
Janssen-Ortho Inc.
Lake Chemicals Pvt Ltd.
Lake Erie Medical and Surgical Supply
Liberty Pharmaceuticals
Major Pharmaceuticals
McNeil Laboratories
Medique Products
Medisca Inc.
Mylan
Novopharm Ltd.
Nucare Pharmaceuticals Inc.
Palmetto Pharmaceuticals Inc.
PCA LLC
PD-Rx Pharmaceuticals Inc.
Perrigo Co.
Pharmacia Inc.
Physicians Total Care Inc.
Preferred Pharmaceuticals Inc.
Prepackage Specialists
Prepak Systems Inc.
Qualitest
Redpharm Drug
Remedy Repack
Rugby Laboratories
Sandhills Packaging Inc.
Teva Pharmaceutical Industries Ltd.
Tya Pharmaceuticals
UDL Laboratories
Vangard Labs Inc.

Dosage forms

Form	Route	Strength
Solution	Oral	1 mg/5mL
Tablet, coated	Oral	2 mg/1
Kit	Oral
Solution	Oral	.2 mg
Liquid	Oral	1 mg/5mL
Tablet, film coated	Oral	2 mg/1
Capsule	Oral	2 mg/1
Solution	Oral	1 mg/7.5mL
Tablet, chewable	Oral	2 mg/1
Solution	Oral	2 mg
Tablet	Oral
Tablet, chewable	Oral
Capsule	Oral	2 mg
Liquid	Oral	.2 mg
Capsule, liquid filled	Oral	2 mg/1
Liquid	Oral	1 mg/7.5mL
Solution	Oral	2 mg/10mL
Suspension	Oral	1 mg/7.5mL
Tablet	Oral	2 mg/1
Tablet	Oral	2 mg
Solution	Oral	0.2 mg

Prices

Unit description	Cost	Unit
Loperamide hcl powder	26.01USD	g
Loperamide HCl 2 mg capsule	0.64USD	capsule
Imodium a-d 2 mg caplet	0.49USD	caplet
Imodium advanced caplet	0.46USD	caplet
Imodium ms relief caplet	0.46USD	caplet
Kaopectate 262 mg caplet	0.37USD	caplet
Loperamide 2 mg caplet	0.37USD	caplet
Qc anti-diarrheal adv caplet	0.3USD	caplet
Diamode 2 mg tablet	0.28USD	tablet
Kaopectate 240 mg softgel	0.25USD	softgel capsule
Anti-diarrheal 2 mg caplet	0.18USD	caplet
CVS Pharmacy anti-diarrheal 2 mg caplet	0.14USD	caplet
Kaopectate children's suspension	0.02USD	ml

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
CA2134611	No	2002-12-24	2014-10-28
US6814978	Yes	2004-11-09	2022-02-26
US6103260	No	2000-08-15	2017-07-17

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	222.1	U.S. Patent 3,714,159; 3,884,916.
water solubility	Slight	Not Available
logP	5.5	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.00086 mg/mL	ALOGPS
logP	4.44	ALOGPS
logP	4.77	ChemAxon
logS	-5.7	ALOGPS
pKa (Strongest Acidic)	13.96	ChemAxon
pKa (Strongest Basic)	9.41	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	43.78 Å²	ChemAxon
Rotatable Bond Count	7	ChemAxon
Refractivity	139.32 m³·mol^-1	ChemAxon
Polarizability	52.67 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9878
Blood Brain Barrier	+	0.7709
Caco-2 permeable	+	0.5875
P-glycoprotein substrate	Substrate	0.7476
P-glycoprotein inhibitor I	Inhibitor	0.8277
P-glycoprotein inhibitor II	Inhibitor	0.8387
Renal organic cation transporter	Inhibitor	0.5059
CYP450 2C9 substrate	Non-substrate	0.8057
CYP450 2D6 substrate	Non-substrate	0.5315
CYP450 3A4 substrate	Substrate	0.7918
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.9154
CYP450 2D6 inhibitor	Inhibitor	0.8933
CYP450 2C19 inhibitor	Non-inhibitor	0.9026
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.9207
Ames test	Non AMES toxic	0.768
Carcinogenicity	Non-carcinogens	0.8564
Biodegradation	Not ready biodegradable	0.9953
Rat acute toxicity	3.6560 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9461
hERG inhibition (predictor II)	Inhibitor	0.7639

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
MS/MS Spectrum - Quattro_QQQ 10V, Positive	LC-MS/MS	splash10-004i-0000900000-673950710672b433271c
MS/MS Spectrum - Quattro_QQQ 25V, Positive	LC-MS/MS	splash10-014i-0090000000-4b7b347a8b8e9dca406c
MS/MS Spectrum - Quattro_QQQ 40V, Positive	LC-MS/MS	splash10-02t9-0090000000-31f15df976e23e73330a
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	LC-MS/MS	splash10-004i-0000900000-d91d13c4e4665bd5fb5a
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	LC-MS/MS	splash10-004i-0020900000-f1be3181a6918c985ffd
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	LC-MS/MS	splash10-014i-0090000000-e5e41346303f41f65688
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	LC-MS/MS	splash10-014i-0090000000-acd8b87c1338e5d0fe25
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	LC-MS/MS	splash10-014i-0090000000-81b85f788d14641430fd
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-014i-0090000000-3ce1a89454d777268799
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , Positive	LC-MS/MS	splash10-03di-0090000000-f101d63ad0bf8e5d2178
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-004i-0000900000-d91d13c4e4665bd5fb5a
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-004i-0020900000-f1be3181a6918c985ffd
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-0090000000-e5e41346303f41f65688
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-0090000000-acd8b87c1338e5d0fe25
LC-MS/MS Spectrum - LC-ESI-QQ , positive	LC-MS/MS	splash10-014i-0090000000-81b85f788d14641430fd
LC-MS/MS Spectrum - LC-ESI-IT , positive	LC-MS/MS	splash10-014i-0090000000-1a1a49f09397ad090e82
MS/MS Spectrum - , positive	LC-MS/MS	splash10-016r-0090600000-794ea6214c0cd97c73fa
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-016r-0090300000-e11942e343a28799a5ab
1H NMR Spectrum	1D NMR	Not Applicable
[1H,13C] 2D NMR Spectrum	2D NMR	Not Applicable

Taxonomy

Description: This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom: Organic compounds
Super Class: Benzenoids
Class: Benzene and substituted derivatives
Sub Class: Diphenylmethanes
Direct Parent: Diphenylmethanes
Alternative Parents: Phenylpiperidines / Phenylacetamides / Aralkylamines / Chlorobenzenes / Aryl chlorides / N-acyl amines / Tertiary carboxylic acid amides / Tertiary alcohols / Trialkylamines / Amino acids and derivatives
show 6 more
Substituents: Diphenylmethane / Phenylpiperidine / Phenylacetamide / Chlorobenzene / Aralkylamine / Halobenzene / Aryl chloride / Aryl halide / Piperidine / N-acyl-amine
show 22 more
Molecular Framework: Aromatic heteromonocyclic compounds
External Descriptors: piperidines, tertiary alcohol, monocarboxylic acid amide, monochlorobenzenes (CHEBI:6532)

Targets

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	58	N/A	N/A	15456245
Ki (nM)	0.53	N/A	N/A	15454210

Details1. Mu-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Voltage-gated calcium channel activity
Specific Function: Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone...
Gene Name: OPRM1
Uniprot ID: P35372
Uniprot Name: Mu-type opioid receptor
Molecular Weight: 44778.855 Da

References

DeHaven-Hudkins DL, Burgos LC, Cassel JA, Daubert JD, DeHaven RN, Mansson E, Nagasaka H, Yu G, Yaksh T: Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther. 1999 Apr;289(1):494-502. [PubMed:10087042]
Tan-No K, Niijima F, Nakagawasai O, Sato T, Satoh S, Tadano T: Development of tolerance to the inhibitory effect of loperamide on gastrointestinal transit in mice. Eur J Pharm Sci. 2003 Nov;20(3):357-63. [PubMed:14592702]
Roge J, Baumer P, Berard H, Schwartz JC, Lecomte JM: The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double-blind, controlled clinical trial versus loperamide. Scand J Gastroenterol. 1993 Apr;28(4):352-4. [PubMed:8488368]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E: Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8. [PubMed:6319884]
di Bosco AM, Grieco P, Diurno MV, Campiglia P, Novellino E, Mazzoni O: Binding site of loperamide: automated docking of loperamide in human mu- and delta-opioid receptors. Chem Biol Drug Des. 2008 Apr;71(4):328-35. doi: 10.1111/j.1747-0285.2008.00637.x. Epub 2008 Feb 12. [PubMed:18284554]

Details2. Delta-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Opioid receptor activity
Specific Function: G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine n...
Gene Name: OPRD1
Uniprot ID: P41143
Uniprot Name: Delta-type opioid receptor
Molecular Weight: 40368.235 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Giagnoni G, Casiraghi L, Senini R, Revel L, Parolaro D, Sala M, Gori E: Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8. [PubMed:6319884]
di Bosco AM, Grieco P, Diurno MV, Campiglia P, Novellino E, Mazzoni O: Binding site of loperamide: automated docking of loperamide in human mu- and delta-opioid receptors. Chem Biol Drug Des. 2008 Apr;71(4):328-35. doi: 10.1111/j.1747-0285.2008.00637.x. Epub 2008 Feb 12. [PubMed:18284554]

Details3. Kappa-type opioid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Opioid receptor activity
Specific Function: G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synt...
Gene Name: OPRK1
Uniprot ID: P41145
Uniprot Name: Kappa-type opioid receptor
Molecular Weight: 42644.665 Da

References

DeHaven-Hudkins DL, Burgos LC, Cassel JA, Daubert JD, DeHaven RN, Mansson E, Nagasaka H, Yu G, Yaksh T: Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther. 1999 Apr;289(1):494-502. [PubMed:10087042]

Details4. Voltage-dependent P/Q-type calcium channel subunit alpha-1A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Voltage-gated calcium channel activity
Specific Function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name: CACNA1A
Uniprot ID: O00555
Uniprot Name: Voltage-dependent P/Q-type calcium channel subunit alpha-1A
Molecular Weight: 282362.39 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
Church J, Fletcher EJ, Abdel-Hamid K, MacDonald JF: Loperamide blocks high-voltage-activated calcium channels and N-methyl-D-aspartate-evoked responses in rat and mouse cultured hippocampal pyramidal neurons. Mol Pharmacol. 1994 Apr;45(4):747-57. [PubMed:8183255]

Details5. Pro-opiomelanocortin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Modulator

General Function: Type 4 melanocortin receptor binding
Specific Function: ACTH stimulates the adrenal glands to release cortisol.MSH (melanocyte-stimulating hormone) increases the pigmentation of skin by increasing melanin production in melanocytes.Beta-endorphin and Met...
Gene Name: POMC
Uniprot ID: P01189
Uniprot Name: Pro-opiomelanocortin
Molecular Weight: 29423.72 Da

References

Nomura A, Iwasaki Y, Aoki Y, Yamamori E, Mutsuga N, Yoshida M, Asai M, Oiso Y, Saito H: Effects of loperamide and other opioid-related substances on the transcriptional regulation of the rat pro-opiomelanocortin gene in AtT20 cells. Neuroendocrinology. 2001 Aug;74(2):87-94. [PubMed:11474216]
Auernhammer CJ, Stalla GK, Lange M, Pfeiffer A, Muller OA: Effects of loperamide on the human hypothalamo-pituitary-adrenal axis in vivo and in vitro. J Clin Endocrinol Metab. 1992 Aug;75(2):552-7. [PubMed:1322429]
Ambrosi B, Bochicchio D, Ferrario R, Colombo P, Faglia G: Effects of the opiate agonist loperamide on pituitary-adrenal function in patients with suspected hypercortisolism. J Endocrinol Invest. 1989 Jan;12(1):31-5. [PubMed:2545766]
Ambrosi B, Bochicchio D, Colombo P, Ferrario R, Faglia G: Loperamide modifies but does not block the corticotropin-releasing hormone-induced ACTH response in patients with Addison's disease. Horm Metab Res Suppl. 1987;16:74-5. [PubMed:2832297]
Bochicchio D, Ambrosi B, Faglia G: Loperamide, an opiate analog, differently modifies the adrenocorticotropin responses to corticotropin-releasing hormone and lysine vasopressin in patients with Addison's disease. Neuroendocrinology. 1988 Dec;48(6):611-4. [PubMed:2855105]

Details6. Calmodulin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Titin binding
Specific Function: Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name: CALM1
Uniprot ID: P0DP23
Uniprot Name: Calmodulin
Molecular Weight: 16837.47 Da

References

Daly JW, Harper J: Loperamide: novel effects on capacitative calcium influx. Cell Mol Life Sci. 2000 Jan 20;57(1):149-57. [PubMed:10949586]
Suzuki T, Sakai H, Ikari A, Takeguchi N: Inhibition of thromboxane A(2)-induced Cl(-) secretion by antidiarrhea drug loperamide in isolated rat colon. J Pharmacol Exp Ther. 2000 Oct;295(1):233-8. [PubMed:10991984]
Mellstrand T: Loperamide--an opiate receptor agonist with gastrointestinal motility effects. Scand J Gastroenterol Suppl. 1987;130:65-6. [PubMed:2820051]
Stoll R, Ruppin H, Domschke W: Calmodulin-mediated effects of loperamide on chloride transport by brush border membrane vesicles from human ileum. Gastroenterology. 1988 Jul;95(1):69-76. [PubMed:2836258]
Diener M, Knobloch SF, Rummel W: Action of loperamide on neuronally mediated and Ca2+- or cAMP-mediated secretion in rat colon. Eur J Pharmacol. 1988 Aug 2;152(3):217-25. [PubMed:2851449]

Details7. Nuclear receptor subfamily 1 group I member 3

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Curator comments: Inverse agonist at the canonical form of the receptor. Likely an antagonist at isoform 3 of the receptor.

General Function: Zinc ion binding
Specific Function: Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name: NR1I3
Uniprot ID: Q14994
Uniprot Name: Nuclear receptor subfamily 1 group I member 3
Molecular Weight: 39942.145 Da

References

Dring AM, Anderson LE, Qamar S, Stoner MA: Rational quantitative structure-activity relationship (RQSAR) screen for PXR and CAR isoform-specific nuclear receptor ligands. Chem Biol Interact. 2010 Dec 5;188(3):512-25. doi: 10.1016/j.cbi.2010.09.018. Epub 2010 Oct 20. [PubMed:20869355]

Enzymes

Details1. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate
Inhibitor

General Function: Vitamin d3 25-hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name: CYP3A4
Uniprot ID: P08684
Uniprot Name: Cytochrome P450 3A4
Molecular Weight: 57342.67 Da

References

Baker DE: Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8. [PubMed:18192961]
Kim KA, Chung J, Jung DH, Park JY: Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. Epub 2004 Sep 8. [PubMed:15365656]
Marechal JD, Yu J, Brown S, Kapelioukh I, Rankin EM, Wolf CR, Roberts GC, Paine MJ, Sutcliffe MJ: In silico and in vitro screening for inhibition of cytochrome P450 CYP3A4 by comedications commonly used by patients with cancer. Drug Metab Dispos. 2006 Apr;34(4):534-8. doi: 10.1124/dmd.105.007625. Epub 2006 Jan 13. [PubMed:16415122]

Details2. Cytochrome P450 2C8

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2C8
Uniprot ID: P10632
Uniprot Name: Cytochrome P450 2C8
Molecular Weight: 55824.275 Da

References

Kim KA, Chung J, Jung DH, Park JY: Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. Epub 2004 Sep 8. [PubMed:15365656]

Details3. Cytochrome P450 2B6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name: CYP2B6
Uniprot ID: P20813
Uniprot Name: Cytochrome P450 2B6
Molecular Weight: 56277.81 Da

References

Kim KA, Chung J, Jung DH, Park JY: Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. Epub 2004 Sep 8. [PubMed:15365656]

Details4. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Steroid hydroxylase activity
Specific Function: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name: CYP2D6
Uniprot ID: P10635
Uniprot Name: Cytochrome P450 2D6
Molecular Weight: 55768.94 Da

References

Kim KA, Chung J, Jung DH, Park JY: Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004 Oct;60(8):575-81. Epub 2004 Sep 8. [PubMed:15365656]

Transporters

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	2500	N/A	N/A	11964599

Details1. Multidrug resistance protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Wandel C, Kim R, Wood M, Wood A: Interaction of morphine, fentanyl, sufentanil, alfentanil, and loperamide with the efflux drug transporter P-glycoprotein. Anesthesiology. 2002 Apr;96(4):913-20. [PubMed:11964599]
Adachi Y, Suzuki H, Sugiyama Y: Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8. [PubMed:11785684]
Schinkel AH, Wagenaar E, Mol CA, van Deemter L: P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J Clin Invest. 1996 Jun 1;97(11):2517-24. [PubMed:8647944]

Drug created on June 13, 2005 07:24 / Updated on January 18, 2019 21:51

Loperamide

Identification

Structure for Loperamide (DB00836)

Pharmacology

Interactions

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Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

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Enzymes

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Transporters

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