Inhibitory actions of the selective serotonin re-uptake inhibitor citalopram on HERG and ventricular L-type calcium currents

Using whole-cell patch clamp recording of heterologous HERG-mediated currents in transfected mammalian cells, we observed that the selective serotonin re-uptake inhibitor citalopram blocks HERG with an IC50 of 3.97 muM. This is slightly less potent than fluoxetine in our system (IC50 of 1.50 muM). In isolated guinea pig ventricular cardiomyocytes citalopram inhibited L-type calcium current(I-Ca,I-L). The voltage dependence Of I-Ca,(L) inactivation in the presence of 100 muM citalopram was shifted significantly leftward. As a result, the I-Ca,I-L 'window' in citalopram was found to be (a) smaller and (b) left ward-shifted compared to control. The effects of citalopram on both calcium current amplitude and the 101 'window' may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.