2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe) induce adverse cardiac effects in vitro and in vivo.
Action Potentials
Animals
Benzylamines
/ adverse effects
CHO Cells
Cardiotoxicity
Cell Survival
Cricetulus
ERG1 Potassium Channel
/ antagonists & inhibitors
Ethylamines
/ toxicity
Heart Diseases
/ chemically induced
Heart Rate
/ drug effects
Male
Myocytes, Cardiac
/ drug effects
Phenethylamines
/ adverse effects
Psychotropic Drugs
/ adverse effects
Rats, Sprague-Dawley
p21-Activated Kinases
/ metabolism
25C-NBOMe
25D-NBOMe
Cardiotoxicity
PAK1
QT interval
hERG channel
Journal
Toxicology letters
ISSN: 1879-3169
Titre abrégé: Toxicol Lett
Pays: Netherlands
ID NLM: 7709027
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
17
08
2018
revised:
21
11
2018
accepted:
13
01
2019
pubmed:
19
1
2019
medline:
5
3
2019
entrez:
19
1
2019
Statut:
ppublish
Résumé
Two emerging psychoactive substances, 2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe), are being abused, leading to fatal and non-fatal intoxications. However, most of their adverse effects have been reported anecdotally. In the present study, cardiotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, rat electrocardiography (ECG), and human ether-a-go-go-related gene (hERG) assay. Expression levels of p21 (CDC42/RAC)-activated kinase 1 (PAK1), one of known biomarkers for cardiotoxicity, were also analyzed. Both 25D-NBOMe and 25C-NBOMe at 100 μM reduced cell viability in MTT assay. At 2.0 mg/kg and 0.75 mg/kg, they prolonged QT intervals in rat ECG. PAK1 was down-regulated by treatment with these two test compounds. Furthermore, potassium channels were inhibited by 25D-NBOMe treatment in hERG assay. Taken together, these results suggest that both 25D-NBOMe and 25C-NBOMe have potential cardiotoxicity, especially regarding cardiac rhythm. Further studies are needed to confirm the relationship between PAK1 down-regulation and cardiotoxicity.
Identifiants
pubmed: 30658151
pii: S0378-4274(18)31753-3
doi: 10.1016/j.toxlet.2019.01.004
pii:
doi:
Substances chimiques
Benzylamines
0
ERG1 Potassium Channel
0
Ethylamines
0
KCNH2 protein, human
0
Phenethylamines
0
Psychotropic Drugs
0
25D-NBOMe
7RET11HE13
2-(4-chloro-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine
9FGW3C260N
Pak1 protein, rat
EC 2.7.11.1
p21-Activated Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
50-57Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.