Renzapride

Identification

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Name
Renzapride
Accession Number
DB04917
Type
Small Molecule
Groups
Investigational
Description

Renzapride is currently in Phase III clinical development in the United States for the treatment of constipation-predominant irritable bowel syndrome (IBS-C). It has been suggested that renzapride is effective in the treatment of irritable bowel syndrome with alternating stool pattern. It is being developed by Alizyme of the UK.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
9073C0W4E9
CAS number
112727-80-7
Weight
Average: 323.818
Monoisotopic: 323.14005467
Chemical Formula
C16H22ClN3O2
InChI Key
YFUAYKVMQVBSNG-UHFFFAOYSA-N
InChI
InChI=1S/C16H22ClN3O2/c1-22-15-11(4-5-12(18)14(15)17)16(21)19-13-6-8-20-7-2-3-10(13)9-20/h4-5,10,13H,2-3,6-9,18H2,1H3,(H,19,21)
IUPAC Name
4-amino-N-{1-azabicyclo[3.3.1]nonan-4-yl}-3-chloro-2-methoxybenzamide
SMILES
COC1=C(C=CC(N)=C1Cl)C(=O)NC1CCN2CCCC1C2

Pharmacology

Indication

For the treatment of constipation-predominant irritable bowel syndrome (IBS-C).

Pharmacodynamics

Renzapride is a substituted benzamide which acts on the upper gastrointestinal tract. It has been shown to enhance stomach emptying in normal subjects; doses of 2 and 5 mg decreasing by 21 and 37% respectively the volume of gastric contents aspirated 80 min after a test meal. Renzapride was found to reduce the oro-caecal transit time as assessed by the lactulose/breath hydrogen method in a dose related manner from 0.2 to 5 mg; the later dose producing a 62% reduction.

Mechanism of action

Renzapride is a full serotonin 5-HT4 receptor agonist and partial serotonin 5-HT3 receptor antagonist.

TargetActionsOrganism
U5-hydroxytryptamine receptor 3ANot AvailableHumans
U5-hydroxytryptamine receptor 4Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
CarisoprodolThe risk or severity of adverse effects can be increased when Carisoprodol is combined with Renzapride.
ClonidineThe risk or severity of sedation can be increased when Clonidine is combined with Renzapride.
EsketamineThe risk or severity of adverse effects can be increased when Renzapride is combined with Esketamine.
EszopicloneThe risk or severity of CNS depression can be increased when Renzapride is combined with Eszopiclone.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
Not Available

References

General References
  1. Staniforth DH, Pennick M: Human pharmacology of renzapride: a new gastrokinetic benzamide without dopamine antagonist properties. Eur J Clin Pharmacol. 1990;38(2):161-4. [PubMed:2338113]
  2. Mackie AD, Ferrington C, Cowan S, Merrick MV, Baird JD, Palmer KR: The effects of renzapride, a novel prokinetic agent, in diabetic gastroparesis. Aliment Pharmacol Ther. 1991 Apr;5(2):135-42. [PubMed:1888816]
  3. Craig DA, Clarke DE: Peristalsis evoked by 5-HT and renzapride: evidence for putative 5-HT4 receptor activation. Br J Pharmacol. 1991 Mar;102(3):563-4. [PubMed:1364818]
  4. Tack J, Middleton SJ, Horne MC, Piessevaux H, Bloor JS, Meyers NL, Palmer RM: Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1655-65. [PubMed:16696817]
External Links
PubChem Compound
3052778
PubChem Substance
175426902
ChemSpider
2314555
Wikipedia
Renzapride

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentIrritable Bowel Syndrome (IBS)1
3TerminatedNot AvailableConstipation-predominant Irritable Bowel Syndrome (IBS-C)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.195 mg/mLALOGPS
logP2.29ALOGPS
logP1.14ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)14.68ChemAxon
pKa (Strongest Basic)8.8ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area67.59 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity88.74 m3·mol-1ChemAxon
Polarizability33.47 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.994
Blood Brain Barrier+0.9483
Caco-2 permeable+0.5727
P-glycoprotein substrateSubstrate0.7809
P-glycoprotein inhibitor INon-inhibitor0.5268
P-glycoprotein inhibitor IINon-inhibitor0.7462
Renal organic cation transporterInhibitor0.5414
CYP450 2C9 substrateNon-substrate0.8584
CYP450 2D6 substrateSubstrate0.5485
CYP450 3A4 substrateSubstrate0.7339
CYP450 1A2 substrateNon-inhibitor0.5744
CYP450 2C9 inhibitorNon-inhibitor0.5085
CYP450 2D6 inhibitorInhibitor0.6059
CYP450 2C19 inhibitorInhibitor0.7174
CYP450 3A4 inhibitorInhibitor0.5694
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6351
Ames testAMES toxic0.6043
CarcinogenicityNon-carcinogens0.9105
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5563 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8478
hERG inhibition (predictor II)Inhibitor0.8497
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 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
3-halobenzoic acids and derivatives / Aminophenyl ethers / Methoxyanilines / Benzamides / Phenoxy compounds / Methoxybenzenes / Anisoles / Benzoyl derivatives / Alkyl aryl ethers / Chlorobenzenes
show 11 more
Substituents
Aminobenzamide / 3-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzamide / Aminophenyl ether / Methoxyaniline / Anisole / Phenoxy compound / Benzoyl / Phenol ether
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel 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. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. Tack J, Middleton SJ, Horne MC, Piessevaux H, Bloor JS, Meyers NL, Palmer RM: Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1655-65. [PubMed:16696817]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. Craig DA, Clarke DE: Peristalsis evoked by 5-HT and renzapride: evidence for putative 5-HT4 receptor activation. Br J Pharmacol. 1991 Mar;102(3):563-4. [PubMed:1364818]

Drug created on October 21, 2007 16:23 / Updated on June 04, 2019 06:13