Identification

Name
Prucalopride
Accession Number
DB06480
Type
Small Molecule
Groups
Approved
Description

Prucalopride (brand name Resolor, developed by Johnson & Johnson and licensed to Movetis) is a drug acting as a selective, high affinity 5-HT4 receptor agonist which targets the impaired motility associated with chronic constipation, thus normalising bowel movements. Prucalopride was approved for use in Europe in 2009 and in Canada (named Resotran) on December 7, 2011 but it has not been approved by the Food and Drug Administration for use in the United States. The drug has also been tested for the treatment of chronic intestinal pseudo-obstruction.

Structure
Thumb
Synonyms
Not Available
External IDs
R-093877 / R093877
Product Ingredients
IngredientUNIICASInChI Key
Prucalopride hydrochlorideM8IYX9Z79V179474-80-7KKMOQGWTJRGLNN-UHFFFAOYSA-N
Prucalopride succinate4V2G75E1CK179474-85-2QZRSNVSQLGRAID-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ResotranTablet1 mgOralJanssen Pharmaceuticals2012-01-12Not applicableCanada
ResotranTablet2 mgOralJanssen Pharmaceuticals2012-01-12Not applicableCanada
International/Other Brands
Resolor
Categories
UNII
0A09IUW5TP
CAS number
179474-81-8
Weight
Average: 367.87
Monoisotopic: 367.1662694
Chemical Formula
C18H26ClN3O3
InChI Key
ZPMNHBXQOOVQJL-UHFFFAOYSA-N
InChI
InChI=1S/C18H26ClN3O3/c1-24-9-2-6-22-7-3-12(4-8-22)21-18(23)14-11-15(19)16(20)13-5-10-25-17(13)14/h11-12H,2-10,20H2,1H3,(H,21,23)
IUPAC Name
4-amino-5-chloro-N-[1-(3-methoxypropyl)piperidin-4-yl]-2,3-dihydro-1-benzofuran-7-carboxamide
SMILES
COCCCN1CCC(CC1)NC(=O)C1=C2OCCC2=C(N)C(Cl)=C1

Pharmacology

Indication

Investigated for use/treatment in constipation, ileus, and pediatric indications.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Prucalopride (PRU) is a selective high affinity 5-HT4 agonist, which are involved in initiating peristalsis. Prucalopride alters colonic motility patterns via serotonin 5-HT4 receptor stimulation: it stimulates colonic mass movements, which provide the main propulsive force for defecation.

TargetActionsOrganism
A5-hydroxytryptamine receptor 4
agonist
Human
Absorption

Prucalopride is rapidly absorbed (Cmax attained 2–3 hours after single 2 mg oral dose) and is extensively distributed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

In vitro, human liver metabolism is very slow and only minor amounts of metabolites are found.

Route of elimination
Not Available
Half life

Terminal half-life is 24–30 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe serum concentration of Prucalopride can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Prucalopride can be increased when it is combined with Acetaminophen.
AfatinibThe serum concentration of Prucalopride can be increased when it is combined with Afatinib.
AgmatineThe therapeutic efficacy of Prucalopride can be decreased when used in combination with Agmatine.
AlbendazoleThe serum concentration of Prucalopride can be increased when it is combined with Albendazole.
AlectinibThe serum concentration of Prucalopride can be increased when it is combined with Alectinib.
AlfentanilThe serum concentration of Prucalopride can be increased when it is combined with Alfentanil.
Aluminum hydroxideThe therapeutic efficacy of Prucalopride can be decreased when used in combination with Aluminum hydroxide.
AmantadineThe serum concentration of Prucalopride can be increased when it is combined with Amantadine.
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Prucalopride.
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
3052762
PubChem Substance
310264873
ChemSpider
2314539
BindingDB
50122872
ChEBI
135552
ChEMBL
CHEMBL117287
Wikipedia
Prucalopride
ATC Codes
A06AX05 — Prucalopride
AHFS Codes
  • 56:92.00 — Miscellaneous GI Drugs

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableOccasional Constipation1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHepatic Impairment1
1CompletedTreatmentOccasional Constipation4
1, 2CompletedNot AvailableFunctional Constipation1
2CompletedTreatmentChronic Constipation1
2CompletedTreatmentOccasional Constipation5
2CompletedTreatmentPostoperative paralytic ileus1
2Enrolling by InvitationTreatmentIneffective Esophageal Motility / Swallowing Disorders1
2, 3RecruitingTreatmentDiabetes Mellitus (DM) / Gastroparesis1
3CompletedDiagnosticBowel preparation therapy / Colon Capsule Completion Times1
3CompletedDiagnosticColon Capsule Completion Rates / Colon Capsule Polyp Detection / Quality of Bowel Preparation for the Colon Capsule1
3CompletedTreatmentChronic Constipation2
3CompletedTreatmentFunctional Constipation1
3CompletedTreatmentMale Subjects With Chronic Constipation1
3CompletedTreatmentOccasional Constipation8
3RecruitingPreventionPostoperative Complications / Postoperative paralytic ileus / Surgery, Colorectal1
3TerminatedTreatmentNon-cancer Pain / Opioid Induced Constipation (OIC)1
4CompletedOtherChronic Constipation1
4CompletedTreatmentChronic Constipation1
4CompletedTreatmentOccasional Constipation2
4Not Yet RecruitingTreatmentCrohn's Disease (CD) / Gluten Enteropathy / Hemorrhage, Gastrointestinal / Inflammatory Bowel Diseases (IBD) / Intestinal Diseases1
4RecruitingTreatmentGastroparesis1
4RecruitingTreatmentPostoperative paralytic ileus1
4WithdrawnNot AvailableChronic Constipation1
Not AvailableCompletedTreatmentOccasional Constipation1
Not AvailableNot Yet RecruitingBasic ScienceAntidepressive Agents / Cognition / Depression / Depressive Disorders / Molecular Mechanisms of Pharmacological Action / Moods Disorders / Psychiatric Disorder NOS1
Not AvailableSuspendedNot AvailableOccasional Constipation1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral1 mg
TabletOral2 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.129 mg/mLALOGPS
logP2.09ALOGPS
logP0.74ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)14.64ChemAxon
pKa (Strongest Basic)8.98ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area76.82 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity100.67 m3·mol-1ChemAxon
Polarizability39.08 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminobenzamides. These are organic compounds containing a benzamide moiety with an amine group attached to the benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Aminobenzamides
Alternative Parents
Coumarans / Alkyl aryl ethers / Piperidines / Aryl chlorides / Trialkylamines / Secondary carboxylic acid amides / Amino acids and derivatives / Oxacyclic compounds / Dialkyl ethers / Azacyclic compounds
show 5 more
Substituents
Aminobenzamide / Coumaran / Alkyl aryl ether / Aryl chloride / Aryl halide / Piperidine / Amino acid or derivatives / Carboxamide group / Secondary carboxylic acid amide / Tertiary aliphatic amine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR4
Uniprot ID
Q13639
Uniprot Name
5-hydroxytryptamine receptor 4
Molecular Weight
43760.975 Da
References
  1. Briejer MR, Bosmans JP, Van Daele P, Jurzak M, Heylen L, Leysen JE, Prins NH, Schuurkes JA: The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound. Eur J Pharmacol. 2001 Jun 29;423(1):71-83. [PubMed:11438309]

Drug created on March 19, 2008 10:34 / Updated on September 22, 2018 22:34