PDF(Pubmed)
Abstract：
BACKGROUND: The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as \"Moxy\") is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects.
OBJECTIVE: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01-30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01-10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT).
RESULTS: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound.
CONCLUSIONS: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field.
OBJECTIVE: Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01-30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01-10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT).
RESULTS: This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound.
CONCLUSIONS: Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field.
摘要：
背景：5-甲氧基-N-甲基-N-异丙基色胺（5-MeO-MiPT，在网上被称为“Moxy”）是一种新的迷幻色胺，于2014年在意大利国家领土上首次发现。它的致幻剂作用广为人知；然而，关于其药物毒理学作用的信息很少。
目的：在Carabinieri臂缉获这种新的精神活性物质并发生人类中毒病例后，在当前的研究中，我们的目标是表征全身给药5-MeO-MiPT（0.01-30mg/kgi.p.）对感觉运动（视觉，声学,和整体触觉)反应，体温调节,和刺激CD-1雄性小鼠的运动活动(阻力和加速度测试)。我们还评估了感觉门控的变化(PPI，前脉冲抑制；0.01-10mg/kgi.p.）和心肺参数（MouseOx和BP-2000；30mg/kgi.p.）。最后,我们研究了计算机模拟ADMET(吸收，分布，新陈代谢，排泄,毒性)与5-甲氧基-N相比，5-MeO-MiPT的概况，N-二异丙基色胺(5-MeO-DIPT)和N,N-二甲基色胺(DMT)。
结果：这项研究表明，5-MeO-MiPT剂量依赖性地抑制感觉运动和PPI反应，在高剂量下，诱导小鼠刺激的运动活动和心肺变化的损害。计算机预测显示,5-MeO-MiPT毒代动力学谱与5-MeO-DIPT和DMT具有相似性,并且突出了与该化合物相关的细胞色素风险。
结论：消耗5-MeO-MiPT会影响进行活动的能力，并对人类健康状况构成风险，正如在小鼠中诱导的效应和中毒病例中发生的症状之间的对应关系所表明的那样。然而,我们的研究结果表明,5-MeO-MiPT不应被排除在精神病治疗领域的研究之外.
目的：在Carabinieri臂缉获这种新的精神活性物质并发生人类中毒病例后，在当前的研究中，我们的目标是表征全身给药5-MeO-MiPT（0.01-30mg/kgi.p.）对感觉运动（视觉，声学,和整体触觉)反应，体温调节,和刺激CD-1雄性小鼠的运动活动(阻力和加速度测试)。我们还评估了感觉门控的变化(PPI，前脉冲抑制；0.01-10mg/kgi.p.）和心肺参数（MouseOx和BP-2000；30mg/kgi.p.）。最后,我们研究了计算机模拟ADMET(吸收，分布，新陈代谢，排泄,毒性)与5-甲氧基-N相比，5-MeO-MiPT的概况，N-二异丙基色胺(5-MeO-DIPT)和N,N-二甲基色胺(DMT)。
结果：这项研究表明，5-MeO-MiPT剂量依赖性地抑制感觉运动和PPI反应，在高剂量下，诱导小鼠刺激的运动活动和心肺变化的损害。计算机预测显示,5-MeO-MiPT毒代动力学谱与5-MeO-DIPT和DMT具有相似性,并且突出了与该化合物相关的细胞色素风险。
结论：消耗5-MeO-MiPT会影响进行活动的能力，并对人类健康状况构成风险，正如在小鼠中诱导的效应和中毒病例中发生的症状之间的对应关系所表明的那样。然而,我们的研究结果表明,5-MeO-MiPT不应被排除在精神病治疗领域的研究之外.
