title: The effect of paroxetine on ouabain-induced toxicity in isolated guinea pig atria.
abstract: It has been reported that selective serotonin reuptake inhibitors (SSRIs) possess some cardiac effects. In the present study we have investigated the effect of paroxetine (PX), a potent SSRI agent, on spontaneously as well as ouabain-induced arrhythmia beating isolated guinea-pig atria. The Guinea-pig heart was rapidly removed; the auricles were dissected out in oxygenated modified Krebs solution. The rate and force of spontaneous contractions were recorded isometrically with a photosensitive transducer. PX (1-16 µg/ml) caused a dose-dependent decrease in the rate of contractions (14-70%) and contractile force (8-16%). Ouabain alone (1.2 µg/ml) produced arrhythmia at 7.2 ± 1.5 min and asystole at 20.1 ± 3.1 min. Pretreatment with PX (4 µg/ml) significantly increased the time of arrhythmia onset to 19.8 min. In addition, PX prolonged the duration of action beating from 20.1 ± 3.1 min to 43.1± 2.6 and delayed the occurrence of asystole. The pattern of contractile force by PX + ouabain treatment was more regular than that observed after administration of ouabain alone. The above findings may the probably be due to the inhibition of cardiac Na(+) and Ca(2+) channels or autonomic nervous system. Results also suggest that PX may reduce the membrane conductance through inhibition of ionic channels to prevent ouabain-induced arrhythmia.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mir-Jamal
authors.initials: MJ
authors.lastname: Hosseini
authors.forename: Azam
authors.initials: A
authors.lastname: Bakhtiarian
authors.forename: Peyvand
authors.initials: P
authors.lastname: Bina
authors.forename: Sima
authors.initials: S
authors.lastname: Sabzeh-Khah
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Najar
authors.forename: Abbas
authors.initials: A
authors.lastname: Pousti
mesh_terms: D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010042:Ouabain / Q000633:toxicity*; D017374:Paroxetine / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D010042:Ouabain; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors