Pharmacological Research 52 (2005) 151–153 The effect of fluvoxamine on ouabain-induced arrhythmia in isolated guinea-pig atria Abbas Pousti ∗ , Tara Deemyad, Kaveh Brumand, Azam Bakhtiarian Department of Pharmacology, Tehran University of Medical Sciences, Tehran, Iran Accepted 21 January 2005 Abstract The effect of fluvoxamine (FLV) a selective serotonin reuptake inhibitor agent was studied on ouabain-induced arrhythmia in spontaneously beating isolated guinea-pig atria. FLV (8–64 M) caused a dose-dependent decrease in the rate of contractions (7–52%) and in the contractile force (11–57%). Ouabain alone (2 M) produced arrhythmia at 4.6 min and asystole at 17.4 min. Pre-administration of the atria with FLV (32 M) significantly increased the time required to produce arrhythmia by ouabain to 14.6 min, prolonged the beating of atria to more than 58.6 min and delayed the occurrence of asystolia. The pattern of contractile force induced by FLV + ouabain was more regular than that produced by ouabain alone. These findings indicate that FLV produces direct cardiac action, probably due to the inhibition of cardiac Na + and Ca 2+ channels. Our results suggest that FLV may reduce the membrane conduction through inhibition of ionic channels which decrease ouabain-induced arrhythmia. © 2005 Elsevier Ltd. All rights reserved. Keywords: Fluvoxamine; Ouabain; Arrhythmia; Isolated atria 1. Introduction It has been reported that tricyclic antidepressant drugs (TCA), such as imipramine and amitriptyline have a quinidine-like effect on both atrial and ventricular arrhyth- mia in therapeutic concentration [1,2]. The newer antidepressant compounds, selective serotonin reuptake inhibitor (SSRI) drugs are widely used as antide- pressants in treating patients. It is thought that by block- ing 5-HT reuptake from nerve terminals and enhancing 5- serotonergic transmission which is regarded as primary ther- apeutic action of these compounds [3]. Recent studies have indicated, however that SSRIs has ad- ditional effects that are apparently not related to the inhibition of the neuronal 5-HT reuptake, for example in cardiac and vascular tissue fluoxetine has been reported to block sodium, calcium and potassium channels [4–7]. ∗ Corresponding author. Tel.: +98 216112803; fax: +98 216402569. E-mail address: drpousti@yahoo.com (A. Pousti). In animal study, specially designed to study the car- diac effect of fluvoxamine (FLV), they have found that FLV produced a decrease in heart rate and a related pro- longation of the QT-interval. The myocardial contractile force (as measured by left ventricular dp/dt) was decreased slightly by FLV and arrhythmia sporadically at nearly lethal dose [8,9]. In man, FLV also produced a statistically sig- nificant slowing of the sinus rate and prolongation the QT interval in relation to the slowing of the heart rate [10]. Although this new antidepressant drug, FLV with high doses has occasionally arrhythmogenic effects, but in our primitive experiments we have found that FLV like fluoxetine and citalopram [11,12] has an antiarrhythmic effect on atria. The primary goal of present study is to elucidate the recently observed important antiarrhythmic activity of this compound in arrhythmia produced by ouabain in isolated guinea-pig atria and discuss the mechanism beyond the phe- nomenon. 1043-6618/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2005.01.002