Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

Arıcı, Aylin; Kalkan, Şule; Demir, Ömer; Aksay, Nil Hocaoglu; Gidener, Sedef; Tunçok, Yeşim

doi:10.1016/j.toxlet.2009.01.015

Cited by 6 publications

(6 citation statements)

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“…3 Additionally, the adenosine A 1 receptor antagonist, DPCPX, was found to shorten the QRS prolongation induced by amitriptyline in an isolated rat heart model. 4,5 These results showed that adenosine A 1 receptor stimulation and/or endogenous adenosine may have a role in amitriptyline-induced QRS prolongation.…”

Section: Introductionmentioning

confidence: 82%

“…3 Kalkan et al showed that hypotension and QRS prolongation by amitriptyline poisoning in rats were reverted by selective adenosine A 1 and A 2a receptor antagonists (DPCPX and CSC, respectively). 3 –5 Furthermore, in another study, it was found that the QRS prolongation developed by amitriptyline was diminished by specific adenosine A 1 receptor antagonist (DPCPX). 4 In an isolated rat heart study, Akgun Arici et al suggested that adenosine A 1 receptor stimulation that causes β-adrenergic receptor (β-AR) blockade may have a role in amitriptyline-induced QRS prolongation.…”

Section: Discussionmentioning

confidence: 99%

“…It did not cause any change in the cardiovascular parameters. 3 –5…”

Section: Methodsmentioning

confidence: 99%

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The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium

et al. 2012

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We investigated the role of adenosine receptors in amitriptyline-induced cardiac action potential (AP) changes in isolated rat atria. In the first group, APs were recorded after cumulative addition of amitriptyline (1 μM, 10 μM and 50 μM). In other groups, each atrium was incubated with selective adenosine A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 10(-4) M) or selective adenosine A(2a) receptor antagonist (8-(3-chlorostyryl) caffeine, 10(-5) M) before amitriptyline administration. Resting membrane potential, AP amplitude (APA), AP duration at 50% and 80% of repolarization (APD(50) and APD(80), respectively), and the maximum rise and decay slopes of AP were recorded. Amitriptyline (50 μM) prolonged the APD(50) and APD(80) (p < 0.001) and the maximum rise slope of AP was reduced by amitriptyline (p < 0.0001). Amitriptyline reduced maximum decay slope of AP only at 50 μM (p < 0.01). DPCPX significantly decreased the 50-μM amitriptyline-induced APD(50) and APD(80) prolongation (p < 0.001). DPCPX significantly prevented the effects of amitriptyline (1 μM and 50 μM) on maximum rise slope of AP (p < 0.05). DPCPX significantly prevented the amitriptyline-induced (50 μM) reduction in maximum decay slope of AP (p < 0.001). The selective adenosine A(1) receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP. A(1) receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.

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Section: Introductionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium

et al. 2012

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“…It was also suggested from multiple sources that some antidepressants (citalopram, amitriptyline) may cause QRS/QT prolongation activating A 1 AdRs. Cardiovascular toxicity was reversed, when AdR antagonists were employed …”

Section: Organ‐specific Toxicity Of Adenosine Derivatives and Adenosimentioning

confidence: 99%

Safety issues of compounds acting on adenosinergic signalling

Schmidt

Ferk

2017

Journal of Pharmacy and Pharmacology

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Objectives Much research has been performed on the field of identifying the roles of adenosine and adenosinergic signalling, but a relatively low number of marketing authorizations have been granted for adenosine receptor (AdR) ligands. In part, this could be related to their safety issues; therefore, our aim was to examine the toxicological and adverse effects data of different compounds acting on adenosinergic signalling, including different AdR ligands and compounds resembling the structure of adenosine. We also wanted to present recent pharmaceutical developments of experimental compounds that showed promising results in clinical trial setting. Key findings Safety issues of compounds modulating adenosinergic signalling were investigated, and different mechanisms were presented. Structurally different classes of compounds act on AdRs, the most important being adenosine, adenosine derivatives and other non-nucleoside compounds. Many of them are either not selective enough or are targeting other targets of adenosinergic signalling such as metabolizing enzymes that regulate adenosine levels. Many other targets are also involved that are not part of adenosinergic signalling system such as GABA receptors, different channels, enzymes and others. Some synthetic AdR ligands even showed to be genotoxic. Summary Current review presents safety data of adenosine, adenosine derivatives and other non-nucleoside compounds that modulate adenosinergic signalling. We have presented different mechanisms that participate to an adverse effect or toxic outcome. A separate section also deals with possible organ-specific toxic effects on different in-vitro and in-vivo models.

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“…[678910] There is only one experimental study about the role of adenosine in cardiovascular effects of the citalopram. [11] It was observed that the negative inotropic and chronotropic effects induced by citalopram can be explained by the inhibition of re-uptake of adenosine or the activation of adenosine A 1 receptors.…”

Section: Introductionmentioning

confidence: 99%

The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity

et al. 2014

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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; A1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A2a 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 A1 receptors without affecting the release of adenosine.

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Does adenosine A1 receptor stimulation causes QRS prolongation by blocking beta adrenergic receptors in amitriptyline poisoning?

Cited by 6 publications

References 20 publications

The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium

The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium

Safety issues of compounds acting on adenosinergic signalling

The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity

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