Premium
Inhibitory actions of the selective serotonin re‐uptake inhibitor citalopram on HERG and ventricular L‐type calcium currents
Author(s) -
Witchel Harry J,
Pabbathi Vijay K,
Hofmann Giovanna,
Paul Ashok A,
Hancox Jules C
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)03320-8
Subject(s) - citalopram , herg , chemistry , pharmacology , serotonin , patch clamp , calcium , serotonin reuptake inhibitor , medicine , electrophysiology , endocrinology , potassium channel , biochemistry , receptor , organic chemistry
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 IC 50 of 3.97 μM. This is slightly less potent than fluoxetine in our system (IC 50 of 1.50 μM). In isolated guinea pig ventricular cardiomyocytes citalopram inhibited L‐type calcium current ( I Ca,L ). The voltage dependence of I Ca,L inactivation in the presence of 100 μM citalopram was shifted significantly leftward. As a result, the I Ca,L ‘window’ in citalopram was found to be (a) smaller and (b) leftward‐shifted compared to control. The effects of citalopram on both calcium current amplitude and the I Ca,L ‘window’ may help to explain citalopram's good cardiac safety profile, given its propensity to block HERG at excessive dosages.