Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, The Netherlands.
Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht University, The Netherlands; Neurotoxicology Research Group, Division Toxicology, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.177, NL-3508 TD, Utrecht, The Netherlands.
Pharmacol Ther. 2018 Feb;182:193-224. doi: 10.1016/j.pharmthera.2017.10.022. Epub 2017 Oct 31.
The use of new psychoactive substances (NPS) is increasing and currently >600 NPS have been reported. However, limited information on neuropharmacological and toxicological effects of NPS is available, hampering risk characterization. We reviewed the literature on the in vitro neuronal modes of action to obtain effect fingerprints of different classes of illicit drugs and NPS. The most frequently reported NPS were selected for review: cathinones (MDPV, α-PVP, mephedrone, 4-MEC, pentedrone, methylone), cannabinoids (JWH-018), (hallucinogenic) phenethylamines (4-fluoroamphetamine, benzofurans (5-APB, 6-APB), 2C-B, NBOMes (25B-NBOMe, 25C-NBOMe, 25I-NBOMe)), arylcyclohexylamines (methoxetamine) and piperazine derivatives (mCPP, TFMPP, BZP). Our effect fingerprints highlight the main modes of action for the different NPS studied, including inhibition and/or reversal of monoamine reuptake transporters (cathinones and non-hallucinogenic phenethylamines), activation of 5-HTreceptors (hallucinogenic phenethylamines and piperazines), activation of cannabinoid receptors (cannabinoids) and inhibition of NDMA receptors (arylcyclohexylamines). Importantly, we identified additional targets by relating reported effect concentrations to the estimated human brain concentrations during recreational use. These additional targets include dopamine receptors, α- and β-adrenergic receptors, GABAreceptors and acetylcholine receptors, which may all contribute to the observed clinical symptoms following exposure. Additional data is needed as the number of NPS continues to increase. Also, the effect fingerprints we have obtained are still incomplete and suffer from a large variation in the reported effects and effect sizes. Dedicated in vitro screening batteries will aid in complementing specific effect fingerprints of NPS. These fingerprints can be implemented in the risk assessments of NPS that are necessary for eventual control measures to reduce Public Health risks.
新精神活性物质（NPS）的使用正在增加，目前已报告超过 600 种 NPS。然而，关于 NPS 的神经药理学和毒理学效应的信息有限，这阻碍了风险特征的描述。我们回顾了关于体外神经元作用模式的文献，以获得不同类别的非法药物和 NPS 的效应指纹。选择最常报道的 NPS 进行审查：苯丙胺（MDPV、α-PVP、甲卡西酮、4-MEC、戊基酮、甲基酮）、大麻素（JWH-018）、（致幻性）苯乙胺（4-氟苯丙胺、苯并呋喃（5-APB、6-APB）、2C-B、NBOMe（25B-NBOMe、25C-NBOMe、25I-NBOMe））、芳基环己基胺（甲氧基甲苯）和哌嗪衍生物（mCPP、TFMPP、BZP）。我们的效应指纹突出了研究的不同 NPS 的主要作用模式，包括单胺再摄取转运体的抑制和/或逆转（苯丙胺和非致幻性苯乙胺）、5-HT 受体的激活（致幻性苯乙胺和哌嗪）、大麻素受体的激活（大麻素）和 NMDA 受体的抑制（芳基环己基胺）。重要的是，我们通过将报告的效应浓度与娱乐性使用期间估计的人类大脑浓度相关联，确定了其他靶点。这些额外的靶点包括多巴胺受体、α-和β-肾上腺素能受体、GABAA 受体和乙酰胆碱受体，这些靶点可能都有助于解释暴露后观察到的临床症状。随着 NPS 数量的不断增加，还需要更多的数据。此外，我们获得的效应指纹仍然不完整，并且报告的效应和效应大小存在很大差异。专门的体外筛选电池将有助于补充 NPS 的特定效应指纹。这些指纹可以应用于 NPS 的风险评估中，这对于最终采取控制措施减少公共卫生风险是必要的。
