Extrapolation of Nonclinical Cardiovascular Study Data to Human –An Example of the 5-HT₄ Receptor Agonist–

Abstract

We exemplify a 5-HT₄ receptor agonist, to compare the Cardiovascular (CV) effects between nonclinical and clinical studies. In the nonclinical studies, the 5-HT₄ receptor agonist showed weak or no effects in in vitro assays, or on in vivo electrocardiograms or blood pressure, whereas dose-dependent increase in heart rate (HR) was noted. Although no CV effects were found in a phase I clinical trial, slight increase in HR was seen in the thorough QT study. The HR increase might be due to on-targeted action to the 5-HT₄ receptor.

The deep prediction of the CV risk from nonclinical studies into human is very important to be carried out, by considering MoA or comparing that with reference compounds, etc.