{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T17:02:40Z","timestamp":1791910960899,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T00:00:00Z","timestamp":1592438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["038570\/Z\/93\/Z"],"award-info":[{"award-number":["038570\/Z\/93\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012068","name":"Health and Care Research Wales","doi-asserted-by":"publisher","award":["SRL\u201019\u201018"],"award-info":[{"award-number":["SRL\u201019\u201018"]}],"id":[{"id":"10.13039\/100012068","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Resurgence in the use of chloroquine as a potential treatment for COVID\u201019 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>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\u2010anaesthetised rats and rabbits. Randomised, controlled treatment studies in rats assessed diazepam, clonazepam and Ro5\u20104864 administered: (i) prior, (ii) during and (iii) after chloroquine and the effects of diazepam: (iv) at high dose, (v) in urethane\u2010anaesthetised rats and (vi) co\u2010administered with adrenaline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Chloroquine decreased the developed tension of left atria, prolonged the effective refractory period of atria, ventricular tissue and right papillary muscles, and caused dose\u2010dependent impairment of haemodynamic and electrocardiographic parameters. Cardiac arrhythmias indicated impairment of atrioventricular conduction. Studies (i), (ii) and (v) showed no differences between treatments 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Neither diazepam nor other ligands for benzodiazepine binding sites protect against or attenuate chloroquine cardiotoxicity. However, diazepam may augment the effects of positive inotropes in reducing chloroquine cardiotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed issue on The Pharmacology of COVID\u201019. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.21\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v177.21\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15101","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T09:55:06Z","timestamp":1589622906000},"page":"4975-4989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Acute chloroquine poisoning: A comprehensive experimental toxicology assessment of the role of diazepam"],"prefix":"10.1111","volume":"177","author":[{"given":"Dyfrig A.","family":"Hughes","sequence":"first","affiliation":[{"name":"Centre for Health Economics and Medicines Evaluation Bangor University  Bangor Wales UK"},{"name":"Department of Molecular and Clinical Pharmacology University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Agence R\u00e9gionale de Sant\u00e9. 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