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
Structure for Piboserod (DB04873)
- 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).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism U5-hydroxytryptamine receptor 4 Not Available Humans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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
- 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]
- 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]
- External Links
- PubChem Compound
- 177336
- PubChem Substance
- 175426880
- ChemSpider
- 154413
- BindingDB
- 85026
- ChEMBL
- CHEMBL356359
- ZINC
- ZINC000001537633
- Wikipedia
- Piboserod
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Prevention Atrial Fibrillation 1 2 Completed Treatment Congestive 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
Property Value Source Water Solubility 0.0287 mg/mL ALOGPS logP 3.54 ALOGPS logP 3 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 14.25 Chemaxon pKa (Strongest Basic) 9.8 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 46.5 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 108.77 m3·mol-1 Chemaxon Polarizability 44.36 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9879 Caco-2 permeable - 0.5086 P-glycoprotein substrate Substrate 0.6484 P-glycoprotein inhibitor I Non-inhibitor 0.5322 P-glycoprotein inhibitor II Non-inhibitor 0.9065 Renal organic cation transporter Inhibitor 0.5265 CYP450 2C9 substrate Non-substrate 0.8053 CYP450 2D6 substrate Non-substrate 0.6806 CYP450 3A4 substrate Substrate 0.5508 CYP450 1A2 substrate Non-inhibitor 0.5245 CYP450 2C9 inhibitor Non-inhibitor 0.8401 CYP450 2D6 inhibitor Non-inhibitor 0.5841 CYP450 2C19 inhibitor Non-inhibitor 0.8026 CYP450 3A4 inhibitor Non-inhibitor 0.7774 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5715 Ames test Non AMES toxic 0.5 Carcinogenicity Non-carcinogens 0.8529 Biodegradation Not ready biodegradable 0.866 Rat acute toxicity 2.6798 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.826 hERG inhibition (predictor II) Non-inhibitor 0.6021
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
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
- 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]
- 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