Piboserod

Identification

Generic Name
Piboserod
DrugBank Accession Number
DB04873
Background

Piboserod (SB 207266) is a selective 5-HT(4) receptor antagonist.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 369.5004
Monoisotopic: 369.241627251
Chemical Formula
C22H31N3O2
Synonyms
  • Piboserod
External IDs
  • 207266
  • SB 207266
  • SB-207266

Pharmacology

Indication

For the treatment of atrial fibrillation and irritable bowel syndrome (IBS).

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Pharmacodynamics

GlaxoSmithKline was investigating piboserod, a 5HT4 antagonist, for the treatment of atrial fibrillation. Phase II trials were ongoing in March 2004, but by December of that year, development had been discontinued. Piboserod had previously being investigated for the treatment of irritable bowel syndrome (IBS), but development for this indication was terminated in 1999.

Mechanism of action

Piboserod appears to act as a specific antagonist of one of the receptors for 5-hydroxytryptamine, the 5-HT4 receptor. The 5-HT4 receptor antagonists are thought to antagonize both the ability of serotonin to sensitize the peristaltic reflex and 5-HT-induced defecation, at least in animal studies. As 5-HT4 receptors are present in human atrial cells and when stimulated may cause atrial arrhythmias, piboserod was under investigation in clinical trials for atrial fibrillation.

TargetActionsOrganism
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as indolecarboxamides and derivatives. These are compounds containing a carboxamide group attached to an indole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Indolecarboxylic acids and derivatives
Direct Parent
Indolecarboxamides and derivatives
Alternative Parents
Indoles / Pyrrole carboxamides / Alkyl aryl ethers / Substituted pyrroles / Benzenoids / Piperidines / Vinylogous amides / Heteroaromatic compounds / Trialkylamines / Amino acids and derivatives
show 6 more
Substituents
Alkyl aryl ether / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carboxamide group / Carboxylic acid derivative / Ether / Heteroaromatic compound
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4UQ3S81B25
CAS number
152811-62-6
InChI Key
KVCSJPATKXABRQ-UHFFFAOYSA-N
InChI
InChI=1S/C22H31N3O2/c1-2-3-11-24-13-9-17(10-14-24)16-23-21(26)20-18-7-4-5-8-19(18)25-12-6-15-27-22(20)25/h4-5,7-8,17H,2-3,6,9-16H2,1H3,(H,23,26)
IUPAC Name
N-[(1-butylpiperidin-4-yl)methyl]-2H,3H,4H-[1,3]oxazino[3,2-a]indole-10-carboxamide
SMILES
CCCCN1CCC(CNC(=O)C2=C3OCCCN3C3=CC=CC=C23)CC1

References

General References
  1. Darblade B, Behr-Roussel D, Gorny D, Lebret T, Benoit G, Hieble JP, Brooks D, Alexandre L, Giuliano F: Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle. World J Urol. 2005 Jun;23(2):147-51. Epub 2005 May 18. [Article]
  2. Armstrong SR, McCullough JL, Beattie DT: Measurement of 5-HT4 receptor-mediated esophageal responses by digital sonomicrometry in the anesthetized rat. J Pharmacol Toxicol Methods. 2006 May-Jun;53(3):198-205. Epub 2005 Sep 15. [Article]
PubChem Compound
177336
PubChem Substance
175426880
ChemSpider
154413
BindingDB
85026
ChEMBL
CHEMBL356359
ZINC
ZINC000001537633
Wikipedia
Piboserod

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedPreventionAtrial Fibrillation1
2CompletedTreatmentCongestive Heart Failure (CHF)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 Solubility0.0287 mg/mLALOGPS
logP3.54ALOGPS
logP3Chemaxon
logS-4.1ALOGPS
pKa (Strongest Acidic)14.25Chemaxon
pKa (Strongest Basic)9.8Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area46.5 Å2Chemaxon
Rotatable Bond Count6Chemaxon
Refractivity108.77 m3·mol-1Chemaxon
Polarizability44.36 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9879
Caco-2 permeable-0.5086
P-glycoprotein substrateSubstrate0.6484
P-glycoprotein inhibitor INon-inhibitor0.5322
P-glycoprotein inhibitor IINon-inhibitor0.9065
Renal organic cation transporterInhibitor0.5265
CYP450 2C9 substrateNon-substrate0.8053
CYP450 2D6 substrateNon-substrate0.6806
CYP450 3A4 substrateSubstrate0.5508
CYP450 1A2 substrateNon-inhibitor0.5245
CYP450 2C9 inhibitorNon-inhibitor0.8401
CYP450 2D6 inhibitorNon-inhibitor0.5841
CYP450 2C19 inhibitorNon-inhibitor0.8026
CYP450 3A4 inhibitorNon-inhibitor0.7774
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5715
Ames testNon AMES toxic0.5
CarcinogenicityNon-carcinogens0.8529
BiodegradationNot ready biodegradable0.866
Rat acute toxicity2.6798 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.826
hERG inhibition (predictor II)Non-inhibitor0.6021
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/MSsplash10-00di-0009000000-ed6d8954d42db3c326c2
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0009000000-8e1ae3fc73e031308546
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0009000000-d669e812c470d7721fec
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0109000000-ce3c5b8eb0c104f12717
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0922000000-715a8ed3642e9b4e2a3b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-000l-3489000000-bf4baa38628af77537a2
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-193.29405
predicted
DeepCCS 1.0 (2019)
[M+H]+195.87416
predicted
DeepCCS 1.0 (2019)
[M+Na]+204.61928
predicted
DeepCCS 1.0 (2019)

Targets

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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. Darblade B, Behr-Roussel D, Gorny D, Lebret T, Benoit G, Hieble JP, Brooks D, Alexandre L, Giuliano F: Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle. World J Urol. 2005 Jun;23(2):147-51. Epub 2005 May 18. [Article]
  2. McCullough JL, Armstrong SR, Hegde SS, Beattie DT: The 5-HT2B antagonist and 5-HT4 agonist activities of tegaserod in the anaesthetized rat. Pharmacol Res. 2006 Apr;53(4):353-8. Epub 2006 Feb 21. [Article]

Drug created at October 20, 2007 11:06 / Updated at February 21, 2021 18:51