In 2002 a research group at the University of Oslo discovered that muscles from the ventricle of failing hearts have increased responsiveness to serotonin. 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.
^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. PMID15365689. S2CID12306762.