Cardiac effects of benzodiazepine receptor agonists and antagonists in the isolated rat heart: A comparative study

Zeegers, A.; Wilgenburg, H. van; Leeuwin, Remy S.

doi:10.1016/s0024-3205(98)00411-1

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…Further, the present study also provides evidence that the specific interaction of diazepam with the coronary arteries in the intact isolated rat heart [34] also applies to the coronary arteries in the endotoxemic isolated rat heart.…”

Section: Discussionsupporting

confidence: 68%

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

Neethling

Hodge

2010

Inflamm. Res.

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Section: Discussionsupporting

confidence: 68%

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

Neethling

Hodge

2010

Inflamm. Res.

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“…Flumazenil reportedly has ambiguous effects on the cardiovascular system. 24,25 The accelerated hemodynamic recovery observed in this study may result from a combination of flumazenil-induced cardiovascular effects and the antagonistic effects of flumazenil on the CNS. The reversibility of flumazenil against the GABA-ergic effects of remimazolam and the related suppression in cardiovascular responses may suggest additional advantages of remimazolam over propofol, since neither the sedating effects nor the cardiovascular effects of propofol are antagonizable by flumazenil or any other antidotes.…”

Section: Discussionmentioning

confidence: 80%

Psychomotor Recovery Following Remimazolam-induced Sedation and the Effectiveness of Flumazenil as an Antidote

Chen

Sang

Song

et al. 2020

Clinical Therapeutics

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“…In view of the fact that the principal adverse effect of chloroquine is negative inotropy (Sofola, 1980) and the absence of positive inotropic effects of diazepam under basal conditions (and negative inotropy under certain conditions [Zeegers, van Wilgenburg, & Leeuwin, 1998]), the use of a positive inotrope seems essential for the improvement in the cardiac function following chloroquine toxicity.…”

Section: Discussionmentioning

confidence: 99%

Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam

Hughes

2020

British J Pharmacology

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of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conflict of interest statement:The author declares no conflicts of interest. Declaration of transparency and scientific rigour:This Declaration acknowledges that this paper adheres to the principles for transparent reporting and scientific rigour of preclinical research as stated in the BJP guidelines for Design and Analysis, and Animal Experimentation, and as recommended by funding agencies, publishers and other organisations engaged with supporting research. AbstractBackground and Purpose: Resurgence in the use of chloroquine as a putative treatment for COVID-19 has seen recent cases of fatal toxicity due to unintentional overdoses. Protocols for the management of poisoning recommend diazepam, although there are uncertainties in its pharmacology and efficacy in this context. The aim was to assess the effects of diazepam in experimental models of chloroquine cardiotoxicity. Experimental Approach:In vitro experiments involved cardiac tissues isolated from rats and incubated with chloroquine, alone, or in combination with diazepam. In vivo models of toxicity involved chloroquine administered intravenously to pentobarbitone-anaesthetised rats and rabbits.Randomised, controlled interventional studies in rats assessed diazepam, clonazepam and Ro5-4864 administered: (i) prior, (ii) during, and (iii) after chloroquine; and the effects of diazepam: (iv) at high dose, (v) in urethane-anaesthetised rats, and (vi) co-administered with adrenaline.Key Results: Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose-dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between interventions and control. Diazepam increased heart rate in study (iv) and, as with clonazepam, also prolonged the QTc interval in study (iii). Combined administration of diazepam and adrenaline in study (vi) improved cardiac contractility but caused hypokalaemia. Conclusion and Implications:Neither diazepam, nor other ligands for benzodiazepine binding sites, protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effe This article is protected by copyright. All rights reserved.cts of positive inotropes in reducing chloroquine cardiotoxicity. Abbreviations:COVID-19 coronavirus disease 2019; FDA Food and Drug Administration; TSPO translocator protein;LV dP/dt time derivative of left ventricular pressure; MTBE methyl-tertiary-butyl ether What is already knownAcute chloroquine poisoning manifests as cardiotoxicity and is often managed using diazepam. What this study addsDiazepam does not attenuate the effects of chloroquine in isolated cardiac tissues, nor in vivo. Clinical significanceInotropic support, which is essential ...

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Cardiac effects of benzodiazepine receptor agonists and antagonists in the isolated rat heart: A comparative study

Cited by 12 publications

References 30 publications

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

Psychomotor Recovery Following Remimazolam-induced Sedation and the Effectiveness of Flumazenil as an Antidote

Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam

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