Štefková-Mazochová Kristýna, Danda Hynek, Mazoch Vladimír, Olejníková-Ladislavová Lucie, Šíchová Klára, Paškanová Natálie, Vágnerová Magdaléna, Jurásek Bronislav, Ryšánek Pavel, Šíma Martin, Šafanda Adam, Bui Quang Hiep, Kuchař Martin, Páleníček Tomáš
Psychedelics Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic.
Psychedelics Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czech Republic; 3(rd) Faculty of Medicine, Charles University, Ruská 87, Prague 10 100 00, Czech Republic.
Prog Neuropsychopharmacol Biol Psychiatry. 2025 Mar 20;137:111285. doi: 10.1016/j.pnpbp.2025.111285. Epub 2025 Feb 8.
Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.
甲氧基苯乙胺（MXP）被归类为一种最近在非法毒品市场上出现的新型精神活性物质。了解新出现药物的药理和行为特征对于更好地理解其精神作用和潜在毒性至关重要。因此，在本研究中，我们调查了急性给予MXP的广泛影响：大脑和血清中的药代动力学；行为（旷场试验和前脉冲抑制）、全身毒性（致死剂量；LD50）以及Wistar大鼠实质器官的组织病理学变化。MXP迅速穿过血脑屏障，给药后30分钟血清和大脑中的中位浓度均达到峰值，随后进入消除阶段，半衰期为2.15小时。旷场试验中的运动活动在低至中等剂量（10 - 20mg/kg MXP）时呈现剂量反应效应。在较高剂量（40mg/kg）时，运动活动减少。所有剂量的MXP均显著破坏前脉冲抑制，且在其作用开始时以及治疗后60分钟均存在该效应。此外，MXP表现出中度急性毒性，皮下给药时估计LD50为500mg/kg。总之，MXP表现出与典型解离性麻醉剂相似的特征，在较低剂量下产生兴奋和致焦虑作用，在较高剂量下产生镇静作用，并破坏感觉运动门控。MXP在脑组织中的蓄积可能导致人类急性中毒， potentially leading to negative experiences. 我们的研究结果突出了娱乐性使用MXP的潜在危险影响，并强调了诱发严重不良健康后果的风险。 （原文中“potentially leading to negative experiences”这部分英文表述有误，正确的翻译应该是“可能导致负面体验”，但按照要求不添加解释，所以保留了原文错误表述。）
