title: The Effects of the Adenosine Receptor Antagonists on the Reverse of Cardiovascular Toxic Effects Induced by Citalopram In-Vivo Rat Model of Poisoning.
abstract: BACKGROUND
  Citalopram is a selective serotonin reuptake inhibitor that requires routine cardiac monitoring to prevent a toxic dose. Prolongation of the QT interval has been observed in acute citalopram poisoning. Our previous experimental study showed that citalopram may be lead to QT prolongation by stimulating adenosine A1 receptors without affecting the release of adenosine.
  
  
  OBJECTIVE
  We examined the effects of adenosine receptor antagonists in reversing the cardiovascular toxic effects induced by citalopram in rats.
  
  
  METHODS
  Animal experimentation.
  
  
  METHODS
  Rats were divided into three groups randomly (n=7 for each group). Sodium cromoglycate (20 mg/kg) was administered to all rats to inhibit adenosine A3 receptor mast cell activation. Citalopram toxicity was achieved by citalopram infusion (4 mg/kg/min) for 20 minutes. After citalopram infusion, in the control group (Group 1), rats were given an infusion of dextrose solution for 60 minutes. In treatment groups, the selective adenosine A1 antagonist DPCPX (Group 2, 8-cyclopentyl-1,3-dipropylxanthine, 20 μg/kg/min) or the selective A2a antagonist CSC (Group 3, 8-(3-chlorostyryl)caffeine, 24 μg/kg/min) was infused for 60 minutes. Mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval measurements were followed during the experiment period. Statistical analysis was performed by ANOVA followed by Tukey's multiple comparison tests.
  
  
  RESULTS
  Citalopram infusion reduced MAP and HR and prolonged the QT interval. It did not cause any significant difference in QRS duration in any group. When compared to the control group, DPCPX after citalopram infusion shortened the prolongation of the QT interval after 40, 50 and 60 minutes (p<0.01). DPCPX infusion shortened the prolongation of the QT interval at 60 minutes compared with the CSC group (p<0.05). CSC infusion shortened the prolongation of the QT at 60 minutes compared with the control group (p<0.05).
  
  
  CONCLUSIONS
  DPCPX improved QT interval prolongation in citalopram toxicity. The results of this study show that mechanism of cardiovascular toxicity induced by citalopram may be related adenosine A1 receptor stimulation. Adenosine A1 receptor antagonists may be used for the treatment of citalopram toxicity.
authors.affiliation: Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
authors.forename: Müjgan
authors.initials: M
authors.lastname: Büyükdeligöz
authors.affiliation: Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
authors.forename: Nil
authors.initials: N
authors.lastname: Hocaoğlu
authors.affiliation: Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
authors.forename: Kubilay
authors.initials: K
authors.lastname: Oransay
authors.affiliation: Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
authors.forename: Yeşim
authors.initials: Y
authors.lastname: Tunçok
authors.affiliation: Department of Medical Pharmacology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
authors.forename: Şule
authors.initials: Ş
authors.lastname: Kalkan
keywords: Adenosine receptor antagonists; QT prolongation; cardiovascular toxicity; citalopram; rat