| Literature DB >> 36051668 |
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.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