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- Title
designer benzodiazepine, flubromazepam, induces reward-enhancing and cardiotoxic effects in rodents.
- Authors
Hong, Eunchong; Gu, Sun Mi; Kim, Jin Mook; Yoon, Kyung Sik; Lee, Jin-Moo; Kim, Young-Hoon; Suh, Soo Kyung; Lee, Dohyun; Eom, Heejong; Yun, Jaesuk; Cha, Hye Jin
- 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.
- Subjects
GABA receptors; POTASSIUM channels; RODENTS; BENZODIAZEPINE receptors; HUMAN genes; CONTROLLED substances; CARDIOTOXICITY
- Publication
Toxicology Research, 2022, Vol 11, Issue 4, p644
- ISSN
2045-452X
- Publication type
Academic Journal
- DOI
10.1093/toxres/tfac039