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 Ca2+ 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.
Baldessarini RJ. Drugs and the treatment of psychiatric disorders: depression and anxiety disorder. In: Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th edn., edition. Hardman, J.G., Limbird, L.E. Gilman, A.G. New York: McGraw-Hill; 2001. p. 447-83.
Pacher P, Keckmeti V, Ungvari Z, Korom S. Pankucsi C. Cardiodepressant effects of fluoxetine in isolated heart preparations. Naunyn Schmiedebergs Arch Pharmacol 1998;358 (l2): 641.
Pacher P, Ungvari Z, Nanasi PP, Furst S, Kecskemeti V. Speculations on difference between tricyclic and selective serotonin reuptake inhibitor antidepressants on their cardiac effects. Is there any? Curr Med Chem 1999;6: 469-80.
Pacher P, Ungvari Z, kecskemti V, Koller A. Serotonin reuptake inhibitor, fluoxetine,dilated skeletal muscle arterioles: Possible role of altered Ca2+ sensitivity. Br J Pharmacol 1999;127: 740-6.
Personne M, Sjoberg G, Perssone H. Citalopram overdose: review of cases treated in Swedish hospitals. Clin Toxicol 1997;35: 237-40.
Ellison JM, Milofsky JE, Ely E. Fluoxetine-induced bradycardia and syncope in two patients. J Clin Psychiatry 1990;51:385-6.
Isbister GK, Prior FH, Foy A. Citalopram-induced bradycardia and presyncope. Ann Pharmacol 2001;35:1552-5.
Bourin M,Chue P, Guillon Y. Paroxetine: A Review. CNS Drug Rev 2001; 7:25-46.
Golding M, Kotlyar M, Carson SW, Hoyler S, Lazarus C, Davidson C, Guzzo J, Sontz E, Garbutt JC. Effects of paroxetine on cardiovascular response to mental stress insubjects with a history of coronary artery disease and no psychiatric diagnosis. Psychopharmacol (Berl) 2005; 182:321-6.
Yeragani VK, Pesce V, Pesce V, Jayaraman A, Roose S. Major depression with Ischemic heart disease: Effects of paroxetine and nortriptyline on long-term heart rate variability measures. Biol Psychiatr 2002;52:418-29.
Pousti A, Malihi G, Abdollahi M, Toosi ER. The effect offluoxetine on ouabain- induced arrhythmia in isolated guinea-pig atria. Indian J Pharmacol 2003;35 :55-8.
Pousti A, Deemyad T, Brumand K. The effect of fluvoxamine on ouabain-induced arrhythmia in isolated guinea-pig atria. Pharmacol Res 2005;52:151-3.
Weld FM, Bigger Jr. Electrophysiological effects of imipramine on ovine cardiac Purkinje and ventricular muscle fibers. Circ Res 1980;46:167-75.
Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns? Curr Pharm Des 2004;10: 2463-75.
Vaswani M, Linda FK, Ramesh S. Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharm Biol Psychiatr 2003; 27: 85-102.
Pousti A, Bakhtiarian A, Najafi R Deemyad T, Brumand K, Hosseini MJ. The effect of serteraline on ouabaininduced arrhythmia in isolated guinea-pig atria. Depress Anxiety 2009;26:106-10.
Tucker P, Adamson P, Miranda R Jr Scarborough A, Williams D, Groff J , McLean H.Paroxetine increases heart rate variability in panic disorder. J Clin Psychopharmacol 1997;17:370-6.
Kalyoncu NI, Ozyavuz R, Karaoglu S. Sertraline inhibitsthe contractile responses to noradrenaline, KCl and electrical field stimulationstimulation of rat isolated vas deferens. J Auton Pharmacol 1999;19:365-9.
Huang CJ, Harootunian A, Maher MP, Quan C, Raj CD, McCormack K, Numann R, Negulescu PA, González JE. Characterization of voltage-gated sodium-channel blockers by electrical stimulation and fluorescence detection of membrane potential. Nat Biotechnol 2006;24:439-46.
Yokota S, Ishikura Y , Ono H . Cardiovascular Effects of Paroxetine: a Newly Developed Antidepressant, in Anesthetized Dogs in Comparison with Those of Imipramine, Amitriptyline and Clomipramine. Jpn J Pharmacol 1987;45:335-42.
Yeragani VK, Jampala VC, Sobelewski E, Kay J & Igel G. Effects of paroxetine on heart period variability in patients with panic disorder: a study of holter ECG records. Neuropsychobiol 1999;40():124-8.
Brenner GM. Pharmacology. 1st ed. USA: WB Saunders Co; 2000; 115.
Wilkerson RD. Antiarrhythmic effects of tricyclic antidepressant drugs in ouabain-induced arrhythmias in the dog. J Pharmacol Exp Ther 1978;205:666-74.
Hiemke C , Hartter S. Pharmacokinetics of selective serotonin reuptake inhibitors. Pharmacol Ther 2000;85:11-28.
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Issue | Vol 49, No 4 (2011) | |
Section | Original Article(s) | |
Keywords | ||
Paroxetine Ouabain Arrhythmias cardiac Guinea pigs Atrial |
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