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. 2019

Kyung Sik Yoon, and Jaesuk Yun, and Young-Hoon Kim, and Jisoon Shin, and Sung Jin Kim, and Jung-Wook Seo, and Sung-Ae Hyun, and Soo Kyung Suh, and Hye Jin Cha
National Institute of Drug and Safety Evaluation, Ministry of Food and Drug Safety, Osong, Cheongju, Republic of Korea. Electronic address: kof9696@korea.kr.

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.

UI MeSH Term Description Entries
D008297 Male Males
D010627 Phenethylamines A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed) Phenylethylamines
D011619 Psychotropic Drugs A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). Psychoactive Agent,Psychoactive Agents,Psychoactive Drug,Psychopharmaceutical,Psychopharmaceuticals,Psychotropic Drug,Psychoactive Drugs,Agent, Psychoactive,Agents, Psychoactive,Drug, Psychoactive,Drug, Psychotropic,Drugs, Psychoactive,Drugs, Psychotropic
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D005021 Ethylamines Derivatives of ethylamine (the structural formula CH3CH2NH2).
D006331 Heart Diseases Pathological conditions involving the HEART including its structural and functional abnormalities. Cardiac Disorders,Heart Disorders,Cardiac Diseases,Cardiac Disease,Cardiac Disorder,Heart Disease,Heart Disorder
D006339 Heart Rate The number of times the HEART VENTRICLES contract per unit of time, usually per minute. Cardiac Rate,Chronotropism, Cardiac,Heart Rate Control,Heartbeat,Pulse Rate,Cardiac Chronotropy,Cardiac Chronotropism,Cardiac Rates,Chronotropy, Cardiac,Control, Heart Rate,Heart Rates,Heartbeats,Pulse Rates,Rate Control, Heart,Rate, Cardiac,Rate, Heart,Rate, Pulse
D000072237 ERG1 Potassium Channel One of three members of the ether-a-go-go (EAG) POTASSIUM CHANNELS gene family comprising ether-a-go-go (eag), eag-like (elk) and eag-related (erg) subfamilies. Ether-a-go-go-related gene 1 (ERG1) also known as KCNH2, encodes the pore-forming subunit of a rapidly activating-delayed rectifier potassium channel that plays an essential role in the final repolarization of ventricular action potential. Loss-of-function mutations in human hERG1 is associated with life-threatening ARRHYTHMIA. Ether-A-Go-Go-Related Potassium Channel 1,Kv11.1 Protein-Potassium Channel,Potassium Voltage-Gated Channel, Subfamily H, Member 2,Channel, ERG1 Potassium,Channel, Kv11.1 Protein-Potassium,Ether A Go Go Related Potassium Channel 1,Kv11.1 Protein Potassium Channel,Potassium Channel, ERG1,Protein-Potassium Channel, Kv11.1
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential

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