Literature DB >> 36051668

The designer benzodiazepine, flubromazepam, induces reward-enhancing and cardiotoxic effects in rodents.

Eunchong Hong1, Sun Mi Gu1, Jin Mook Kim2, Kyung Sik Yoon2, Jin-Moo Lee2, Young-Hoon Kim2, Soo Kyung Suh2, Dohyun Lee3, Heejong Eom3, Jaesuk Yun1, Hye Jin Cha4.   

Abstract

The use of many benzodiazepines is controlled worldwide due to their high likelihood of abuse and potential adverse effects. Flubromazepam-a designer benzodiazepine-is a long-acting gamma-aminobutyric acid subtype A receptor agonist. There is currently a lack of scientific evidence regarding the potential for flubromazepam dependence or other adverse effects. This study aimed to evaluate the dependence potential, and cardiotoxicity via confirmation of the QT and RR intervals which are the factors on the electrical properties of the heart of flubromazepam in rodents. Using a conditioned place preference test, we discovered that mice treated intraperitoneally with flubromazepam (0.1 mg/kg) exhibited a significant preference for the flubromazepam-paired compartment, suggesting a potential for flubromazepam dependence. In addition, we observed several cardiotoxic effects of flubromazepam; 100-μM flubromazepam reduced cell viability, increased RR intervals but not QT intervals in the electrocardiography measurements, and considerably inhibited potassium channels in a human ether-à-go-go-related gene assay. Collectively, these findings suggest that flubromazepam may have adverse effects on psychological and cardiovascular health, laying the foundation for further efforts to list flubromazepam as a controlled substance at both national and international levels.
© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Entities:  

Keywords:  cardiotoxicity; conditioned place preference (CPP); dependence potential; electrocardiography (ECG); flubromazepam; gamma-aminobutyric acid subtype A (GABAA); human ether-a-go-go-related gene (hERG); self-administration (SA)

Year:  2022        PMID: 36051668      PMCID: PMC9424716          DOI: 10.1093/toxres/tfac039

Source DB:  PubMed          Journal:  Toxicol Res (Camb)        ISSN: 2045-452X            Impact factor:   2.680


  42 in total

1.  Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics.

Authors:  Bjoern Moosmann; Laura M Huppertz; Melanie Hutter; Armin Buchwald; Sascha Ferlaino; Volker Auwärter
Journal:  J Mass Spectrom       Date:  2013-11       Impact factor: 1.982

2.  Assessment of the Availability, Cost, and Motivations for Use over Time of the New Psychoactive Substances-Benzodiazepines Diclazepam, Flubromazepam, and Pyrazolam-in the UK.

Authors:  Rachelle Abouchedid; Thea Gilks; Paul I Dargan; John R H Archer; David M Wood
Journal:  J Med Toxicol       Date:  2018-04-18

3.  Flubromazolam - Basic pharmacokinetic evaluation of a highly potent designer benzodiazepine.

Authors:  Laura M Huppertz; Bjoern Moosmann; Volker Auwärter
Journal:  Drug Test Anal       Date:  2017-05-19       Impact factor: 3.345

4.  Neural bases for addictive properties of benzodiazepines.

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Authors:  Kyung Sik Yoon; Sun Mi Gu; Santosh Lamichhane; Kyoung Moon Han; Jisoon Shin; Young-Hoon Kim; Soo Kyung Suh; Hye Jin Cha; Jaesuk Yun
Journal:  Cardiovasc Toxicol       Date:  2019-06       Impact factor: 3.231

Review 7.  Risk of arrhythmia induced by psychotropic medications: a proposal for clinical management.

Authors:  Søren Fanoe; Diana Kristensen; Anders Fink-Jensen; Henrik Kjærulf Jensen; Egon Toft; Jimmi Nielsen; Poul Videbech; Steen Pehrson; Henning Bundgaard
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8.  QT Prolongation and Life Threatening Ventricular Tachycardia in a Patient Injected With Intravenous Meperidine (Demerol®).

Authors:  Mi Kyoung Song; Eun Jung Bae; Jae Suk Baek; Bo Sang Kwon; Gi Beom Kim; Chung Il Noh; Jung Yun Choi; Sung Sup Park
Journal:  Korean Circ J       Date:  2011-06-30       Impact factor: 3.243

9.  Life Threatening Severe QTc Prolongation in Patient with Systemic Lupus Erythematosus due to Hydroxychloroquine.

Authors:  John P O'Laughlin; Parag H Mehta; Brian C Wong
Journal:  Case Rep Cardiol       Date:  2016-07-12

10.  Estrogenic activity of zinc pyrithione: an in vivo and in vitro study.

Authors:  Kyung Sik Yoon; Namhee Youn; Hyungyung Gu; Seung Jun Kwack
Journal:  Environ Health Toxicol       Date:  2017-02-09
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