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Cardiotoxic effects of [3-[2-(diethylamino)ethyl]-1H-indol-4-yl] acetate and 3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-ol.
- Source :
-
Toxicology letters [Toxicol Lett] 2020 Feb 01; Vol. 319, pp. 40-48. Date of Electronic Publication: 2019 Nov 06. - Publication Year :
- 2020
-
Abstract
- Two synthetic tryptamines, namely [3-[2-(diethylamino)ethyl]-1H-indol-4-yl] acetate (4-AcO-DET) and 3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-ol (4-HO-MET), are abused by individuals seeking recreational hallucinogens. These new psychoactive substances (NPSs) can cause serious health problems because their adverse effects are mostly unknown. In the present study, we evaluated the cardiotoxicity of 4-AcO-DET and 4-HO-MET using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, electrocardiography (ECG), and the human ether-a-go-go-related gene (hERG) assay. In addition, we analyzed the expression level of p21 (CDC42/RAC)-activated kinase 1 (PAK1), which is known to play various roles in the cardiovascular system. In the MTT assay, 4-AcO-DET- and 4-HO-MET-treated H9c2 cells proliferated in a concentration-dependent manner. Moreover, both substances increased QT intervals (as determined using ECG) in Sprague-Dawley rats and inhibited potassium channels (as verified by the hERG assay) in Chinese hamster ovary cells. However, there was no change in PAK1 expression. Collectively, the results indicated that 4-AcO-DET and 4-HO-MET might cause adverse effects on the cardiovascular system. Further studies are required to confirm the relationship between PAK1 expression and cardiotoxicity. The findings of the present study would provide science-based evidence for scheduling the two NPSs.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
CHO Cells
Cell Line
Cell Survival drug effects
Cricetulus
ERG1 Potassium Channel metabolism
Electrocardiography
Male
Myocytes, Cardiac drug effects
Potassium Channel Blockers toxicity
Rats
Rats, Sprague-Dawley
p21-Activated Kinases biosynthesis
p21-Activated Kinases genetics
Cardiotoxins toxicity
Hallucinogens toxicity
Tryptamines toxicity
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 319
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 31706004
- Full Text :
- https://doi.org/10.1016/j.toxlet.2019.10.022