Serotonin Signalling Outside of the Central Nervous System

The Background

Prof. Levy and co-workers at the University of Oslo discovered that failing cardiac ventricles express 5-HT₄ receptors as a response to the malignant condition. In analogy with adrenergic action on the failing heart, a sensitization to serotonin signaling is expected to have a deteriorating effect on the disease. The research group therefore hypothesized that a 5-HT₄ receptor antagonist could provide additional benefit to long-term disease development.

Clinical Trial

This hypothesis was confirmed in a heart failure model in the rat. In a clinical phase II study of patients with congestive heart failure, the selective 5-HT₄ antagonist piboserod significantly improved Left ventricular Ejection Fraction when treated for 24 weeks on top of evidence based pharmacological treatment.