Piboserod

drugbox


IUPAC_name = "N"-((1-Butyl-4-piperidyl)-methyl)-3,4-dihydro-2"H"-(1,3)oxazino(3,2-a)indole-10-carboxamide
CAS_number = 152811-62-6
PubChem = 177336
C = 22 | H = 31 | N = 3 | O = 2
molecular_weight = 369.50 g/mol
legal_status = Clinical phase II
routes_of_administration = Oral

Piboserod is a selective 5-HT₄ receptor antagonist which was in clinical development by GlaxoSmithKline (GSK) for the management of atrial fibrillation and irritable bowel syndrome. In 2007 the Norwegian company Bio-Medisinsk Innovasjon AS (BMI) [ [http://www.serodus.com Company web-page] ] completed a clinical phase II study to investigate the effect of piboserod in patients with chronic heart failure.

Mechanism of action

In 2002 a research group at the University of Oslo discovered that muscles from the ventricle of failing hearts have increased responsiveness to serotonin. [Bratteli T. et al, Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure. Naunyn-Schmiedeberg's Arch. Pharmacol., 370:157-166, 2004] They later demonstrated that the effect was due to an expression of functional 5-HT₄ receptors in the failing muscle. On the basis of these findings, and in analogy with the success of betablockers in heart failure, the group made the hypothesis that 5-HT₄ receptor antagonists could be useful to treat heart failure. Their hypothesis was tested in animal models of heart failure with positive results. [Birkeland JA. et al, Effects of treatment with a 5-HT4 receptor antagonist in heart failure. Br J Pharmacol. 2007 Jan;150(2):143-52. Epub 2006 Dec 11. ]

References