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
Thumb
Synonyms
  • Loperamid
  • Loperamida
  • Lopéramide
  • Loperamidum
External IDs
PJ 185 / R 18553
Product Ingredients
IngredientUNIICASInChI Key
Loperamide hydrochloride77TI35393C34552-83-5PGYPOBZJRVSMDS-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ImodiumCapsule2 mg/1OralMcNeil Consumer Healthcare2008-02-26Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Loperamide HydrochlorideCapsule2 mg/1OralRemedy Repack2016-02-162016-11-22Us
Loperamide HydrochlorideCapsule2 mg/1OralLake Erie Medical Dba Quality Care Produts Llc2010-10-012014-06-01Us
Loperamide HydrochlorideCapsule2 mg/1OralTeva Pharmaceuticals USA, Inc.1993-05-01Not applicableUs0093 031120180814 13942 1zxdpf
Loperamide HydrochlorideCapsule2 mg/1OralPhysicians Total Care, Inc.1996-06-20Not applicableUs
Loperamide HydrochlorideCapsule2 mg/1OralPd Rx Pharmaceuticals, Inc.1993-05-01Not applicableUs
Loperamide HydrochlorideCapsule2 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs53808 070720180907 15195 1lqlbvf
Loperamide HydrochlorideCapsule2 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs1993-05-01Not applicableUs
Loperamide HydrochlorideCapsule2 mg/1OralNucare Pharmaceuticals, Inc.1993-05-01Not applicableUs
Loperamide HydrochlorideCapsule2 mg/1OralUnit Dose Services1991-09-18Not applicableUs
Loperamide HydrochlorideCapsule2 mg/1OralAmerincan Health Packaging2017-01-09Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
7 Select Anti DiarrhealSolution1 mg/7.5mLOral7-Eleven2018-08-07Not applicableUs
7 Select Anti DiarrhealTablet, film coated2 mg/1Oral7 Eleven2014-08-05Not applicableUs
A DTablet, film coated2 mg/1OralWestern Family Foods2003-04-102017-08-12Us
A DTablet, film coated2 mg/1OralWestern Family Foods2003-02-252017-08-29Us
Alti-loperamide - 2mg CapletTablet2 mgOralAltimed Pharma Inc.1995-12-311997-08-14Canada
Anti DiarrhealTablet, film coated2 mg/1OralKroger2003-02-21Not applicableUs
Anti DiarrhealTablet, film coated2 mg/1OralH.E.B.2014-05-01Not applicableUs
Anti DiarrhealTablet, film coated2 mg/1OralRemedy Repack2016-05-192018-06-05Us
Anti DiarrhealTablet, film coated2 mg/1OralCVS Health2003-02-24Not applicableUs
Anti DiarrhealTablet, film coated2 mg/1OralPublix Supermarkets, Inc.2003-03-19Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Anti Diarrheal and Anti GasLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralWalgreen Company2018-10-10Not applicableUs
Anti Diarrheal Plus Anti GasLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralMeijer Distribution Inc2018-10-16Not applicableUs
Basic Care Loperamide Hydrochloride and SimethiconeLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralL. Perrigo Company2018-10-17Not applicableUs
Dg Health Anti Diarrheal Anti GasLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralDOLGENCORP, LLC2018-10-09Not applicableUs
Doc in the Box All Day SupplyLoperamide 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)KitOralDoc In The Box Llc2018-05-14Not applicableUs
Good Sense Anti Diarrheal Anti GasLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralL Perrigo Company2018-10-11Not applicableUs
Health Mart Anti Diarrheal Anti GasLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)TabletOralMcKesson2018-10-10Not applicableUs
ImodiumLoperamide hydrochloride (2 mg/1) + Dimethicone (125 mg/1)Tablet, chewableOralMc Neil Consumer Healthcare Div. Mc Neil Ppc, Inc2008-08-012014-12-31Us
Imodium Complete CapletsLoperamide hydrochloride (2 mg) + Simethicone (125 mg)TabletOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc2002-06-20Not applicableCanada
Imodium Complete Chewable TabletsLoperamide hydrochloride (2 mg) + Simethicone (125 mg)Tablet, chewableOralMcneil Consumer Healthcare Division Of Johnson & Johnson Inc1998-05-12Not applicableCanada
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.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
ADelta-type opioid receptor
agonist
Human
AKappa-type opioid receptor
agonist
Human
UVoltage-dependent P/Q-type calcium channel subunit alpha-1A
inhibitor
Human
UPro-opiomelanocortin
modulator
Human
UCalmodulin
inhibitor
Human
UNuclear receptor subfamily 1 group I member 3Not AvailableHuman
Absorption

Not significantly absorbed from the gut

Volume of distribution
Not Available
Protein binding

97%

Metabolism

Hepatic

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
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Loperamide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Loperamide.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Loperamide is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Loperamide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Loperamide.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Loperamide.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Loperamide.
6-Deoxyerythronolide BThe metabolism of Loperamide can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Loperamide.
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination 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, combinationsA07DA03 — Loperamide
AHFS Codes
  • 56:08.00 — Antidiarrhea Agents
FDA label
Download (55.5 KB)
MSDS
Download (73.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentPain NOS1
1CompletedBasic ScienceDrug Drug Interaction (DDI)1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceIntestinal Obstruction2
1CompletedTreatmentHealthy Volunteers2
1RecruitingTreatmentNeoplasms, Breast1
2CompletedTreatmentCancer, Breast / Early-Stage Breast Carcinoma / Hormone Receptor Positive Tumor1
2RecruitingSupportive CareMetastatic Colorectal Cancers1
2RecruitingTreatmentEarly Stage HER2+ Breast Cancer1
2RecruitingTreatmentHer2-Positive Breast Cancer1
2WithdrawnTreatmentMalignancies1
2, 3CompletedTreatmentDiarrhoea Predominant Irritable Bowel Syndrome / Functional Diarrhea1
2, 3CompletedTreatmentFemale Genital Diseases1
2, 3CompletedTreatmentIncontinence, Fecal1
2, 3Not Yet RecruitingTreatmentClostridium Difficile Infection (CDI)1
3CompletedSupportive CareColorectal Cancers / Severe or persistent diarrhea1
3CompletedTreatmentIncontinence, Fecal1
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3CompletedTreatmentSevere or persistent diarrhea1
3TerminatedPreventionDehydration, Diverting Ileostomy, Loperamide1
3TerminatedPreventionSevere or persistent diarrhea1
3TerminatedTreatmentEnteritis / Malignancies / Severe or persistent diarrhea1
3TerminatedTreatmentHigh Output Stoma1
3TerminatedTreatmentRectal Carcinoma / Short Bowel Syndrome (SBS) / Ulcerative Colitis (UC)1
4CompletedTreatmentTravelers' Diarrhea1
4CompletedTreatmentSevere or persistent diarrhea3
4RecruitingTreatmentOpiate withdrawal symptoms1
4SuspendedTreatmentAntibiotic Associated Diarrhea / Antibiotic-Associated Diarrhea / Clostridium Difficile1
4TerminatedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
4WithdrawnTreatmentIncontinence, Fecal1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedTreatmentIncontinence, Fecal1
Not AvailableNot Yet RecruitingBasic ScienceIntestinal Transit1
Not AvailableRecruitingTreatmentIncontinence, Fecal1
Not AvailableTerminatedTreatmentIncontinence, Fecal1

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
FormRouteStrength
SolutionOral1 mg/5mL
Tablet, film coatedOral2 mg/1
Tablet, coatedOral2 mg/1
KitOral
SolutionOral.2 mg
LiquidOral1 mg/5mL
CapsuleOral2 mg/1
SolutionOral1 mg/7.5mL
Tablet, chewableOral2 mg/1
SolutionOral2 mg
TabletOral
Tablet, chewableOral
CapsuleOral2 mg
LiquidOral.2 mg
LiquidOral1 mg/7.5mL
Capsule, liquid filledOral2 mg/1
SolutionOral2 mg/10mL
SuspensionOral1 mg/7.5mL
TabletOral2 mg/1
TabletOral2 mg
SolutionOral0.2 mg
Prices
Unit descriptionCostUnit
Loperamide hcl powder26.01USD g
Loperamide HCl 2 mg capsule0.64USD capsule
Imodium a-d 2 mg caplet0.49USD caplet
Imodium advanced caplet0.46USD caplet
Imodium ms relief caplet0.46USD caplet
Kaopectate 262 mg caplet0.37USD caplet
Loperamide 2 mg caplet0.37USD caplet
Qc anti-diarrheal adv caplet0.3USD caplet
Diamode 2 mg tablet0.28USD tablet
Kaopectate 240 mg softgel0.25USD softgel capsule
Anti-diarrheal 2 mg caplet0.18USD caplet
CVS Pharmacy anti-diarrheal 2 mg caplet0.14USD caplet
Kaopectate children's suspension0.02USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2134611No2002-12-242014-10-28Canada
US6814978Yes2004-11-092022-02-26Us
US6103260No2000-08-152017-07-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)222.1U.S. Patent 3,714,159; 3,884,916.
water solubilitySlightNot Available
logP5.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00086 mg/mLALOGPS
logP4.44ALOGPS
logP4.77ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)13.96ChemAxon
pKa (Strongest Basic)9.41ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area43.78 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity139.32 m3·mol-1ChemAxon
Polarizability52.67 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9878
Blood Brain Barrier+0.7709
Caco-2 permeable+0.5875
P-glycoprotein substrateSubstrate0.7476
P-glycoprotein inhibitor IInhibitor0.8277
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterInhibitor0.5059
CYP450 2C9 substrateNon-substrate0.8057
CYP450 2D6 substrateNon-substrate0.5315
CYP450 3A4 substrateSubstrate0.7918
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9154
CYP450 2D6 inhibitorInhibitor0.8933
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9207
Ames testNon AMES toxic0.768
CarcinogenicityNon-carcinogens0.8564
BiodegradationNot ready biodegradable0.9953
Rat acute toxicity3.6560 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9461
hERG inhibition (predictor II)Inhibitor0.7639
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-004i-0000900000-673950710672b433271c
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-014i-0090000000-4b7b347a8b8e9dca406c
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-02t9-0090000000-31f15df976e23e73330a
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, PositiveLC-MS/MSsplash10-004i-0000900000-d91d13c4e4665bd5fb5a
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, PositiveLC-MS/MSsplash10-004i-0020900000-f1be3181a6918c985ffd
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, PositiveLC-MS/MSsplash10-014i-0090000000-e5e41346303f41f65688
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, PositiveLC-MS/MSsplash10-014i-0090000000-acd8b87c1338e5d0fe25
LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, PositiveLC-MS/MSsplash10-014i-0090000000-81b85f788d14641430fd
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-014i-0090000000-3ce1a89454d777268799
LC-MS/MS Spectrum - LC-ESI-IT (LC/MSD Trap XCT, Agilent Technologies) , PositiveLC-MS/MSsplash10-03di-0090000000-f101d63ad0bf8e5d2178
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-0000900000-d91d13c4e4665bd5fb5a
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-0020900000-f1be3181a6918c985ffd
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0090000000-e5e41346303f41f65688
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0090000000-acd8b87c1338e5d0fe25
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0090000000-81b85f788d14641430fd
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-014i-0090000000-1a1a49f09397ad090e82
MS/MS Spectrum - , positiveLC-MS/MSsplash10-016r-0090600000-794ea6214c0cd97c73fa
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-016r-0090300000-e11942e343a28799a5ab
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot 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

Details
1. Mu-type opioid receptor
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  5. 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]
  6. 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]
Kind
Protein
Organism
Human
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
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
Kind
Protein
Organism
Human
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
  1. Daly JW, Harper J: Loperamide: novel effects on capacitative calcium influx. Cell Mol Life Sci. 2000 Jan 20;57(1):149-57. [PubMed:10949586]
  2. 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]
  3. Mellstrand T: Loperamide--an opiate receptor agonist with gastrointestinal motility effects. Scand J Gastroenterol Suppl. 1987;130:65-6. [PubMed:2820051]
  4. 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]
  5. 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]
Kind
Protein
Organism
Human
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
  1. 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

Kind
Protein
Organism
Human
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
  1. Baker DE: Loperamide: a pharmacological review. Rev Gastroenterol Disord. 2007;7 Suppl 3:S11-8. [PubMed:18192961]
  2. 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]
  3. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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]
Kind
Protein
Organism
Human
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
  1. 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

Kind
Protein
Organism
Human
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
  1. 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]
  2. 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]
  3. 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 November 17, 2018 07:13