| RESEARCH ARTICLE
|Year : 2014 | Volume
| Issue : 4 | Page : 378-385
The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity
Kubilay Oransay, Nil Hocaoglu, Mujgan Buyukdeligoz, Yesim Tuncok, Sule Kalkan
Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey
Aim: We investigated the role of adenosine in citalopram-induced cardiotoxicity.
Materials and Methods: Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A 2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour prior to citalopram. Other rats were pretreated with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; inhibitor of adenosine deaminase) and S-(4-Nitrobenzyl)-6-thioinosine (NBTI; inhibitor of facilitated adenosine transport). After pretreatment, group 2 received 5% dextrose and group 3 received citalopram. Adenosine concentrations, mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval were evaluated.
Results: In the dextrose group, citalopram infusion caused a significant decrease in MAP and HR and caused a significant prolongation in QRS and QT. DPCPX infusion significantly prevented the prolongation of the QT interval when compared to control. In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. In EHNA/NBTI groups, citalopram-induced MAP and HR reductions, QRS and QT prolongations were more significant than the dextrose group.
Conclusions: Citalopram may lead to QT prolongation by stimulating adenosine A 1 receptors without affecting the release of adenosine.
Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir
Source of Support: The Scientifi c and Technological Research Council of
Turkey., Conflict of Interest: None
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