The effects of the adenosine receptor antagonists on the reverse of cardiovascular toxic effects induced by citalopram in-vivo rat model of poisoning

Objective: The aim is to investigate the effects of the selective adenosine receptor antagonists in reversing citalopram-induced cardiovascular toxicity.Methods: Citalopram (4 mg/kg/min) was infused to rats after sodium cromoglycate (A3 receptor antagonist, 20 mg/kg intravenously). After the citalopram infusion, 5% dekstrose, DPCPX (8-Cyclopentyl-1,3-Dipropylxanthine; selective adenosine A1 receptor antagonist, 20 ? g/kg/dk) or CSC [8-(3-chlorostyryl) caffeine; selective adenosine A2a receptor antagonist, 24 ?g/kg/min] (n=7, for all groups) were infused for 60 minutes. Mean arterial pressure (MAP), heart rate (HR), QRS and QT durations were recorded. ANOVA followed by Tukey-Kramer test were used for statistical analysis.Results: Citalopram decreased the MAP and HR (p<0.001) and prolonged the QT (p<0.001, p<0.01 and p<0.001 respectively) in all groups. 5% dextrose increased the MAP at 10th, 20th, 30th, 40th, 50th and 60th minutes (p<0.05, p<0.01, p<0.05, p<0.01, p<0.05 and p<0.05; respectively) and HR for all minutes (p<0.001). DPCPX increased the MAP and the HR after the 10th minute (for MAP p<0.01, p<0.001, p<0.001, p<0.01, p<0.01 and p<0.01 and for HR p<0.01, p<0.001, p<0.001, p<0.001, p<0.001 and p<0.001 respectively 10th, 20th, 30th, 40th, 50th and 60th minutes), shortened the QT at the 30th, 40th, 50th and 60th minutes (p<0.05, p<0.05, p<0.05 and p<0.001 respectively). CSC shortened the QT only at 60th minute (p<0.05). DPCPX shortened the QT at the 40th (p<0.01), 50th (p<0.01) and 60th (p<0.001) minutes and CSC shortened the QT at the 60th minute (p<0.05) compared to 5% dextrose.Conclusion: A selective adenosine A1 receptor antagonist, DPCPX, reversed the citalopram-induced decrease in mean arterial pressure and heart rate and QT prolongation in rats. DPCPX reversed the QT prolongation when compared to 5% dextrose. The effects of DPCPX may be explained with physiologic or pharmacologic antagonism.Keywords: Adenosine receptor antagonists, citalopram poisoning, cardiovascular toxicity.