Citalopram is a serotonin-selective re-uptake inhibitor (SSRI) that is effective against depression and that appears to exhibit minimal drug interaction potential (Keller, 2000). In experiments on guinea-pig papillary muscle, citalopram has been reported to produce action potential shortening within a concentration range of 10-100 µM (Pacher et al. 2000). It has been suggested that this effect may in part result from an action of citalopram on channels carrying L-type calcium current (I_Ca,L), although no direct evidence of this has yet been presented (Pacher et al. 2000). The present investigation was therefore undertaken to determine whether or not citalopram exhibits I_Ca,L blocking activity.

Adult male guinea-pigs were killed humanely by cervical dislocation and myocytes were isolated by a combination of mechanical and enzymatic dispersion. Whole-cell recordings of I_Ca,L were made at 37 °C in a K⁺-free external solution, using a Cs⁺-based pipette dialysate. I_Ca,L was elicited by a two-step protocol applied from a holding potential of -80 mV: an initial step to -40 mV for 100 ms activated and inactivated fast sodium current; a second step to +10 mV for 600 ms then elicited I_Ca,L. Citalopram concentrations between 1 and 100 µM inhibited I_Ca,L in a dose-dependent manner; 100 µM citalopram blocked the current by 65 ± 2.3 % (mean ± S.E.M.; n = 7 cells). In further experiments, the voltage dependence of I_Ca,L activation was not significantly altered by 100 µM citalopram (P > 0.2; paired t test; n = 6 cells). However, voltage-dependent inactivation was shifted towards more negative potentials by this citalopram concentration (P < 0.001; n = 8 cells). Our data provide direct evidence for an inhibitory effect of citalopram on guinea-pig ventricular I_Ca,L.This work was supported by the British Heart Foundation (PG/2000123 and PG/98081).

Keller, M.B. (2000). J. Clin. Psychiat. 61, 896-908.

Pacher, P., Bagi, Z., Lako-Futo, Z., Ungvari, Z., Nanasi, P.P. & Kecskemeti, V. (2000). Gen. Pharmacol. 34, 17-23.