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Erschienen in: Forensic Toxicology 1/2020

19.08.2019 | Original Article

Antagonists for serotonin receptors ameliorate rhabdomyolysis induced by 25D-NBOMe, a psychoactive designer drug

verfasst von: Genri Kawahara, Mami S. Nakayashiki, Hideyuki Maeda, Ruri Kikura-Hanajiri, Ken-ichi Yoshida, Yukiko K. Hayashi

Erschienen in: Forensic Toxicology | Ausgabe 1/2020

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Abstract

Purpose

N-Benzyl-substituted phenethylamines (NBOMes) are psychoactive drugs, which induce various symptoms like serotonin syndrome, even at low doses. Recently, we reported the first lethal case of a designer drug, 2-(4-bromo-2, 5-dimethoxyphenyl)-NBOMe (25B-NBOMe) intoxication with severe rhabdomyolysis, evaluated by clinical, pathological, and toxicological analyses. We also confirmed that 25B-NBOMe can induce rhabdomyolysis using a zebrafish model. To further elucidate pathomechanism of NBOMes-induced rhabdomyolysis, we treated zebrafish with a similar designer drug, 2-(4-methyl-2, 5-dimethoxyphenyl)-NBOMe (25D-NBOMe).

Methods

Zebrafish treated with a designer drug, 25D-NBOMe, were examined survival rate and were analyzed skeletal muscle degeneration by birefringence. They were also analyzed expression levels of 5-HT2A and 5-HT2C receptors and ryanodine receptor.

Results

The 25D-NBOMe-treated fish showed decreased survival rate and skeletal muscle degeneration detected by birefringence mimicking to those of 25B-NBOMe-treated fish. We revealed that 25D-NBOMe induced up-regulation of the expression of 5-HT2A and 5-HT2C receptors, and rhabdomyolysis was inhibited by the 5-HT2A receptor antagonist, aripiprazole and 5-HT2C receptor antagonist, SB242084. Moreover, ryanodine receptor expression was up-regulated in 25D-NBOMe-treated fish as compared to that of untreated fish, and the up-regulated expression of ryanodine receptor in 25D-NBOMe-treated fish was improved with co-treatment aripiprazole and SB242084.

Conclusions

Our findings suggest that multiple 5-HT receptors have important roles in NBOMes-induced rhabdomyolysis together with other serotonin-related symptoms. Zebrafish is a highly useful model for therapeutic studies of rhabdomyolysis induced by psychoactive designer drugs.
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Metadaten
Titel
Antagonists for serotonin receptors ameliorate rhabdomyolysis induced by 25D-NBOMe, a psychoactive designer drug
verfasst von
Genri Kawahara
Mami S. Nakayashiki
Hideyuki Maeda
Ruri Kikura-Hanajiri
Ken-ichi Yoshida
Yukiko K. Hayashi
Publikationsdatum
19.08.2019
Verlag
Springer Singapore
Erschienen in
Forensic Toxicology / Ausgabe 1/2020
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-019-00495-w

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