General
Preferred name
PRUCALOPRIDE
Synonyms
R-108512 ()
Resolor Succinate ()
R-93877 ()
R0-93877 ()
prucalopride succinate (IV) ()
Prucalopride (succinate) ()
PRUCALOPRIDE SUCCINATE ()
PRUCALOPRIDA ()
R-093877 ()
RESOLOR ()
R093877 ()
Motegrity ()
Prucalopride (as succinate) ()
P&D ID
PD009298
CAS
179474-81-8
179474-80-7
179474-85-2
Tags
available
drug
Approved by
EMA
FDA
First approval
2009
Drug indication
Constipation
Irritable bowel syndrome
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION
Prucalopride succinate is an orally active, selective and specific 5-HT 4 receptor agonist (high affinity), with pKis of 8.6 and 8.1 for human 5-HT4a/4b receptors, respectively. Prucalopride succinate improves intestinal motility by promoting regeneration of the intestinal nervous system in rats. Prucalopride succinate also shows anticancer activity by blocking of the PI3K/AKT/mTor signaling pathway. Prucalopride succinate can be used in studies of chronic constipation, pseudo-intestinal obstruction and cancer[1][2][3][4].
PRICE
33
MOA
Prucalopride acts as a selective stimulator of the 5-HT4 receptors while having no interaction with hERG channel or 5-HT1 receptors which reduces significantly the cardiovascular risk found in other similar drugs.[A40250]; ; 5-HT4 receptors can be found throughout the gastrointestinal tract primarily in smooth muscle cells, enterochromaffin cells, and myenteric plexus. Its activation produces the release of acetylcholine which is the major excitatory neurotransmitter in the GI tract.[A37348]; ; Hence, prucalopride stimulates motility by interacting specifically with 5-HT4 receptors in the GI tract which causes a release of acetylcholine and further contraction of the muscle layer of the colon and relaxation of the circular muscle layer leading to the propulsion of luminal content.[A14331]
INDICATION
Prucalopride is indicated for the treatment of chronic idiopathic constipation (CIC) in adults.[L4882]; ; CIC is one of the most common chronic functional gastrointestinal disorders worldwide. The diagnosis of this agent is very hard and it can be confirmed if the patient experience at least two of the following:; ; -Straining during more than 25% of the bowel movements.; ; -Lumpy or hard stools in 25% of the bowel movements.; ; -Sensation of incomplete evacuation in more than 25% of all bowel movements.; ; -Sensation of anorectal blockage or obstruction in more than 25% of the bowel movements.; ; -Manual maneuvers required in more than 25% of the bowel movements.; ; -Fewer than 3 bowel movements per week.[L4883]
TOXICITY
Prucalopride is well tolerated in doses reaching 10 times the recommended therapeutic dose and signs of overdose are thought to be stared by the presence of headaches, nausea and diarrhea.[F2384] Carcinogenicity studies in mice indicated an increased incidence of mammary gland adenocarcinoma at a dose of 80 mg/kg/day. In rats, high doses were linked to increased incidence of benign adrenal pheochromocytoma, pituitary adenoma, pancreatic adenoma, hepatocellular adenoma and thyroid follicular tumors.[F2386]; ; For genotoxicity, prucalopride showed only one weak positive result in one of the five bacterial strain reverse mutation test at high concentrations.[F2386] As well, there is no evidence of adverse effects on fertility, even in high doses.[FDA label]
DESCRIPTION
Prucalopride is a serotonin 5-HT4 receptor agonist.
(GtoPdb)
PHARMACODYNAMICS
In animal studies, prucalopride induced a dose-dependent stimulation of contractile activity in the proximal colon and inhibition of the contractility in the distal colon.[A40253] As well it has been shown that prucalopride stimulates and amplifies giant migratory contraction which is the high-amplitude type of contraction that initiates the urge to defecate. Thus, prucalopride not only accelerates the colonic transit but also accelerates gastric emptying and small bowel transit.[A37348] ; ; In supratherapeutic concentrations, prucalopride can be observed to interact with hERG potassium channels and L-type calcium channels.[A37348]; ; In clinical trials, prucalopride showed to significantly increase the spontaneous bowel movements with a standardized mean difference of about 0.5 after the use of 1 mg when compared with the placebo group.[A40254] In this studies as well, it was observed a numerical improvement in mean colonic transit time and a significant increase in spontaneous complete bowel movement without marked changes in the anorectal function.[A40254] ; ; In phase III clinical trials, 86% of the tested individuals opted to continue with the open-label study and based on Patients Assessments, 67% of the patients increase more than one point improvement in their satisfaction.[A40254]; ; In the final set of clinical trials for approval, there was a significant increase in the number of patients that reached over 3 complete spontaneous bowel movements per week when compared with the placebo.[L4882]
DESCRIPTION
Prucalopride is an orally active, selective and specific 5-HT 4 receptor agonist (high affinity), with pKis of 8.6 and 8.1 for human 5-HT4a/4b receptors, respectively. Prucalopride improves intestinal motility by promoting regeneration of the intestinal nervous system in rats. Prucalopride also shows anticancer activity by blocking of the PI3K/AKT/mTor signaling pathway. Prucalopride can be used in studies of chronic constipation, pseudo-intestinal obstruction and cancer[1][2][3].
PRICE
31
DESCRIPTION
Prucalopride Succinate (Resolor Succinate) is a selective, high affinity 5-HT4 receptor agonist, inhibiting human 5-HT(4a) and 5-HT(4b) receptor with Ki value of 2.5 nM and 8 nM, respectively.
(TargetMol Bioactive Compound Library)
DESCRIPTION
Prucalopride is a potent and selective 5-HT4 receptor agonist. Prucalopride is a gastroprokinetic drug with the brand name Resolor, developed for the treatment of constipation and irritable bowel syndrome. Studies indicates that it is promisingly to be a candidate therapy of Alzheimer's disease and chronic intestinal pseudo-obstruction.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
Prucalopride acts as a selective stimulator of the 5-HT4 receptors. It is used to treat adults with chronic idiopathic constipation.
(Enamine Bioactive Compounds)
DESCRIPTION
Prucalopride (R-93877) is a selective, high-affinity 5-HT4A/4B receptor agonist (Ki: 2.5/8 nM). It has >290-fold selectivity for 5-HT4A/4B receptor than other 5-HT receptor subtypes.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
27
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Enamine Bioactive Compounds
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
50
Molecular Weight
367.17
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
6
Ring Count
3
Aromatic Ring Count
1
cLogP
2.09
TPSA
76.82
Fraction CSP3
0.61
Chiral centers
0.0
Largest ring
6.0
QED
0.59
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
5-HT Receptor
5-HT4A
5-HT4B
HTR4
5-HT4 agonist
Apoptosis
Autophagy
Member status
member
MOA
5-HT4 Agonists
serotonin receptor agonist
Indication
constipation
Pathway
GPCR/G protein
Neuronal Signaling
Neuroscience
Recommended Cell Concentration
100 nM
Source data
