4′-Fluoropyrrolidinononanophenone elicits neuronal cell apoptosis through elevating production of reactive oxygen and nitrogen species

Morikawa, Yoshifumi; Miyazono, Hidetoshi; Sakai, Yuji; Suenami, Koichi; Sasajima, Yasuhide; Sato, Kazumi; Takekoshi, Yuji; Monguchi, Yasunari; Ikari, Akira; Matsunaga, Toshiyuki

doi:10.1007/s11419-020-00550-x

Cited by 7 publications

(1 citation statement)

References 44 publications

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“…Common single doses of PV8 are between 20 and 40 mg, but doses as high as approximately 400 mg were also reported [8,162]. Pyrrolidine cathinone derivatives with elongated aliphatic side chains such as PV8 were shown to have high cytotoxicity, which was further increased by the presence of the methylenedioxy grouping (also present in the new MDPV8), and also had fewer psychostimulant effects when taken at the same doses, which may induce users to use them at higher doses, further increasing their harmfulness [163,165,[169][170][171]. Concentrations found in cases of fatal MDPHP poisoning were 7-399 ng/mL in postmortem blood [130,133,172,173], while concentrations of 2-5950 ng/ mL in urine and 3-140 ng/mL in blood were detected in non-fatal intoxications (Table 1) [159,172,174].…”

Section: Mdpv8mentioning

confidence: 99%

A review of synthetic cathinones emerging in recent years (2019–2022)

Kuropka¹,

Zawadzki

Szpot

2022

Forensic Toxicol

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Purpose The emergence of novel psychoactive substances (NPS) has been being a continuous and evolving problem for more than a decade. Every year, dozens of new, previously unknown drugs appear on the illegal market, posing a significant threat to the health and lives of their users. Synthetic cathinones are one of the most numerous and widespread groups among NPS. The purpose of this work was to identify and summarize available data on newly emerging cathinones in very recent years. Methods Various online databases such as PubMed, Google Scholar, but also databases of government agencies including those involved in early warning systems, were used in search of reports on the identification of newly emerging synthetic cathinones. In addition, threads on various forums created by users of these drugs were searched for reports on the effects of these new substances. Results We have identified 29 synthetic cathinones that have been detected for the first time from early 2019 to mid-2022. We described their structures, known intoxication symptoms, detected concentrations in biological material in poisoning cases, as well as the countries and dates of their first appearance. Due to the lack of studies on the properties of the novel compounds, we compared data on the pharmacological profiles of the better-known synthetic cathinones with available information on the newly emerged ones. Some of these new agents already posed a threat, as the first cases of poisonings, including fatal ones, have been reported. Conclusions Most of the newly developed synthetic cathinones can be seen as analogs and replacements for once-popular compounds that have been declining in popularity as a result of legislative efforts. Although it appears that some of the newly emerging cathinones are not widely used, they may become more popular in the future and could become a significant threat to health and life. Therefore, it is important to continue developing early warning systems and identifying new compounds so that their widespread can be prevented.

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Section: Mdpv8mentioning

confidence: 99%

A review of synthetic cathinones emerging in recent years (2019–2022)

Kuropka¹,

Zawadzki

Szpot

2022

Forensic Toxicol

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α-Pyrrolidinooctanophenone facilitates activation of human microglial cells via ROS/STAT3-dependent pathway

Sakai,

Hattori,

Morikawa

et al. 2024

Forensic Toxicol

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Purpose Pyrrolidinophenone derivatives (PPs) are amphetamine-like designer drugs containing a pyrrolidine ring, and their adverse effects resemble those of methamphetamine (METH). Microglial activation has been recently suggested as a key event in eliciting the adverse effects against dysfunction of the central nervous system. The aim of this study is to clarify the mechanisms of microglial activation induced by PPs. Methods We employed the human microglial cell line HMC3 to assess microglial activation induced by PPs and evaluated the capacities for proliferation and interleukin-6 (IL-6) production that are characteristic features of the activation events. Results The WST-1 assay indicated that viability of HMC3 cells was increased by treatment with sublethal concentrations (5–20 µM) of α-pyrrolidinooctanophenone (α-POP), a highly lipophilic PP, whereas it was decreased by treatment with concentrations above 40 µM. Treatment with sublethal α-POP concentrations up-regulated the expression and secretion of IL-6. Additionally, α-POP-induced increase in cell viability was restored by pretreating with N-acetyl-l-cysteine, a reactive oxygen species (ROS) scavenger, and stattic, an inhibitor of signal transducer and activator of transcription 3 (STAT3), respectively, suggesting that activation of the ROS/STAT3 pathway is involved in the α-POP-induced activation of HMC3 cells. The increases in cell viability were also observed in HMC3 cells treated with other α-POP derivatives and METH. Conclusions These results suggest that enhanced productions of ROS and IL-6 are also involved in microglial activation by drug treatment and that HMC3 cell-based system is available to evaluate accurately the microglial activation induced by abused drugs.

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