A case of fatal intoxication due to the new designer drug 25B-NBOMe

Yoshida, Kenichi; Saka, Kanju; Shintani-Ishida, Kaori; Maeda, Hideyuki; Nakajima, Makoto; Hara, Shuichi; Ueno, Makoto; Sasaki, Katsunori; Iwase, Hirotaro; Sakamoto, Tetsuya

doi:10.1007/s11419-015-0276-7

Cited by 23 publications

(12 citation statements)

References 16 publications

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“…Because 45% of the lethal cases of serotonin syndrome presented high serum levels of creatine kinase, rhabdomyolysis may be a predominant cause of death in NBOMe intoxication [ 7 ]. Recently, we reported a case of serotonin syndrome with lethal rhabdomyolysis after the ingestion of 2-(4-bromo-2,5-dimethoxyphenyl)- N -(2-methoxybenzyl) ethanamine (25B-NBOMe), one of the most potent 5-HT 2A agonists with α 1 -adrenoceptor agonist activity [ 8 ]. Prominent rhabdomyolysis was also reported in two other cases with severe 25B-NBOMe intoxication [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

et al. 2017

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N-Benzyl-substituted 2C class phenethylamines (NBOMes) are psychoactive designer drugs, with strong hallucinogenic and stimulant effects, even at low doses. The designer drug, 2-(4-bromo-2, 5-dimethoxyphenyl)-N-(2-methoxybenzyl) ethanamine (25B-NBOMe) is considered to be one of the most potent agonists of the serotonin-2A (5-HT2A) receptor. Recently, we reported the first lethal case of 25B-NBOMe intoxication with severe rhabdomyolysis, concluded by clinical, pathological and toxicological analyses. There are currently no good animal models that closely recapitulate serotonin receptor-dependent rhabdomyolysis. In the present study, we created animal models of rhabdomyolysis using zebrafish larvae to study the pathomechanism of rhabdomyolysis, and demonstrated that 25B-NBOMe can simulate lethal rhabdomyolysis in this animal. Treatment of the larvae with 25B-NBOMe decreased their survival rate, locomotion, altered birefringence of the skeletal muscle and immunostainings for dystroglycan (a myoseptal protein) and myosin heavy chain (a myofibril protein), which were consistent with rhabdomyolysis. This 25B-NBOMe-induced rhabdomyolysis was inhibited by the 5-HT2A receptor antagonists ritanserin and aripirazole, but not by the 5-HT1A + 5-HT1B receptor antagonist propranolol and the 5-HT3 receptor antagonist granisetron, indicating 5-HT2A-dependent rhabdomyolysis. The 25B-NBOMe-treated zebrafish is, therefore, a highly useful model of rhabdomyolysis for studying the pathomechanism of rhabdomyolysis as well as for therapeutic drug screening.

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Section: Introductionmentioning

confidence: 99%

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

et al. 2017

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“…Drug-induced hyperthermia has also been reported in cases using 2-(4-bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe), a substance abused as a recreational drug (Poklis et al, 2014;Yoshida et al, 2015). NBOMes are compounds formed by the addition of a 2-methoxybenzyl group to the 2C family of phenethylamine and act as agonist of 5-HT 2A and 5-HT 2C receptors.…”

Section: Introductionmentioning

confidence: 99%

5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

Nakamura

Shintani-Ishida

Ikegaya

2018

J Pharmacol Exp Ther

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Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5-dimethoxyphenyl)--(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist of 5-HT receptor used as a recreational drug, reportedly induces hyperthermia. This study aimed to verify whether 25B-NBOMe induces ambient temperature-dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague-Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an ambient temperature of 23°C or 29°C. 25B-NBOMe administration at 23°C did not change the core body temperature of the rats, whereas administration at 29°C induced significant hyperthermia 30-120 minutes postadministration. Tail surface temperature temporarily decreased 30 minutes postadministration, indicating heat storage by peripheral vasoconstriction despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was suppressed by sarpogrelate, but not by destruction of central noradrenaline or serotonin neurons, peripheral 5-HT receptors were considered contributors to the development of hyperthermia at a high ambient temperature, independently from central neurons. The temperature of brown adipose tissue (BAT) increased 60-120 minutes postadministration of 25B-NBOMe at 29°C, indicating thermogenesis. Previous studies have reported that peripheral serotonin contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin levels were observed at 29°C, and serotonin administration partially suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature, suggesting that decreased levels of peripheral serotonin induced BAT thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a high ambient temperature via vasoconstriction regulated by 5-HT receptors and BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus, peripheral serotonin plays a partial but important role in thermoregulation.

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“…However, the accumulation of 25B‐NBOMe was approximately six times greater in the lung than in the myocardium. Additionally, in our previous autopsy case, the concentration of 25B‐NBOMe was much higher in the left heart chamber than in this right heart chamber . These results suggest that 25B‐NBOMe can increase postmortem in cardiac blood via redistribution from the lung.…”

Section: Resultsmentioning

confidence: 52%

“…In our previously reported autopsy case, a phenomenon of PMR was observed in a patient whose circulating 25B‐NBOMe was cleared by the time of death 4 days after drug use . To reproduce these findings, the distribution of 25B‐NBOMe in rats 7 days after the drug administration was investigated.…”

Section: Resultsmentioning

confidence: 93%

“…On the fourth day, his plasma 25B-NBOMe concentration was below the limit of quantification (LOQ 0.025 ng/mL). However, the 25B-NBOMe concentration of the postmortem cardiac blood samples approximately 2 days after death increased to 0.36 and 0.18 ng/mL in the left and right heart chambers, respectively (7). As the 25B-NBOMe concentration was higher in the left than in the right heart chamber, this postmortem increase in cardiac blood appeared to be caused by PMR from the lung to the heart (10).…”

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Experimental Study on the Postmortem Redistribution of the Substituted Phenethylamine, 25B‐NBOMe

Shintani-Ishida

Saka

Nakamura

et al. 2017

Journal of Forensic Sciences

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2-(4-Bromo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25B-NBOMe) is a substituted phenethylamine, which has become highly prevalent worldwide since 2014. Recently, in an autopsy case involving fatal 25B-NBOMe intoxication, we found the postmortem increase of 25B-NBOMe concentration in the cardiac blood approximately 2 days after death. The aim of this study was to investigate the distribution of 25B-NBOMe and reproduce the postmortem redistribution using a rat model. Sprague-Dawley rats were killed 30 min after intraperitoneal injection of 25B-NBOMe (0.5 mg/kg) and left for 0, 3, 6, 9, 15, or 24 h (six rats at each time point). Postmortem 25B-NBOMe concentrations in the cardiac blood increased by more than 10-fold at 6-h postmortem. 25B-NBOMe accumulated primarily in the lung. Moreover, this postmortem redistribution occurred even in rats that had died 1 week following the 25B-NBOMe administration. These findings indicate that attention should be paid to sample collection and data interpretation in the toxicological analysis of 25B-NBOMe.

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A case of fatal intoxication due to the new designer drug 25B-NBOMe

Cited by 23 publications

References 16 publications

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

Experimental Study on the Postmortem Redistribution of the Substituted Phenethylamine, 25B‐NBOMe

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A case of fatal intoxication due to the new designer drug 25B-NBOMe

Cited by 23 publications

References 16 publications

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

Experimental Study on the Postmortem Redistribution of the Substituted Phenethylamine, 25B‐NBOMe

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5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature