Piboserod

Piboserod
Clinical data
Trade names	Serlipet
Routes of; administration	Oral
ATC code	none;
Legal status
Legal status	Clinical phase II;
Identifiers
	IUPAC name N-((1-Butyl-4-piperidyl)-methyl)-3,4-dihydro-2H-(1,3)oxazino(3,2-a)indole-10-carboxamide;
CAS Number	152811-62-6 ;
PubChem CID	177336;
IUPHAR/BPS	225;
ChemSpider	154413 ;
UNII	4UQ3S81B25;
ChEMBL	ChEMBL356359 ;
CompTox Dashboard (EPA)	DTXSID60165129 ;
Chemical and physical data
Formula	C22H31N3O2
Molar mass	369.509 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCCN1CCC(CNC(=O)c2c3n(c4ccccc24)CCCO3)CC1;
	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) ; Key:KVCSJPATKXABRQ-UHFFFAOYSA-N ;
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Piboserod is a selective 5-HT₄ receptor antagonist which was marketed and manufactured by GlaxoSmithKline (GSK) under the trade name Serlipet for the management of atrial fibrillation and irritable bowel syndrome. In 2007 the Norwegian company Bio-Medisinsk Innovasjon AS (BMI)^[1] 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.^[2] 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.^[3]

References

^ Company web-page
^ Brattelid T, Qvigstad E, Lynham JA, Molenaar P, Aass H, Geiran O, et al. (September 2004). "Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure". Naunyn-Schmiedeberg's Archives of Pharmacology. 370 (3): 157–66. doi:10.1007/s00210-004-0963-0. PMID 15365689. S2CID 12306762.
^ Birkeland JA, Sjaastad I, Brattelid T, Qvigstad E, Moberg ER, Krobert KA, et al. (January 2007). "Effects of treatment with a 5-HT4 receptor antagonist in heart failure". British Journal of Pharmacology. 150 (2): 143–52. doi:10.1038/sj.bjp.0706966. PMC 2042907. PMID 17160012.

[1] Company web-page

[2] Brattelid T, Qvigstad E, Lynham JA, Molenaar P, Aass H, Geiran O, et al. (September 2004). "Functional serotonin 5-HT4 receptors in porcine and human ventricular myocardium with increased 5-HT4 mRNA in heart failure". Naunyn-Schmiedeberg's Archives of Pharmacology. 370 (3): 157–66. doi:10.1007/s00210-004-0963-0. PMID 15365689. S2CID 12306762.

[3] Birkeland JA, Sjaastad I, Brattelid T, Qvigstad E, Moberg ER, Krobert KA, et al. (January 2007). "Effects of treatment with a 5-HT4 receptor antagonist in heart failure". British Journal of Pharmacology. 150 (2): 143–52. doi:10.1038/sj.bjp.0706966. PMC 2042907. PMID 17160012.

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