Fabregat-Safont David, Barneo-Muñoz Manuela, Carbón Xoán, Hernández Félix, Martinez-Garcia Ferran, Ventura Mireia, Stove Christophe P, Sancho Juan V, Ibáñez María
Environmental and Public Health Analytical Chemistry, Research Institute for Pesticides and Water, Jaume I University, Castellón, Spain.
Predepartmental Unit of Medicine, Unitat Mixta de Neuroanatomia Funcional NeuroFun-UVEG-UJI, Jaume I University, Castellón, Spain.
Addict Biol. 2020 Dec 2:e12979. doi: 10.1111/adb.12979.
Synthetic cathinones are the second most commonly seized new psychoactive substance family in Europe. These compounds have been related to several intoxication cases, including fatalities. Although the pharmacological effects, metabolism, and pharmacokinetics of cathinones have been studied, there is little information about the permeability of these compounds through the blood-brain barrier (BBB). This is an important parameter to understand the behavior and potency of cathinones. In this work, 13 selected cathinones have been analyzed in telencephalon tissue from Sprague-Dawley rats intraperitoneally dosed at 3 mg/kg. Our results revealed a direct relationship between compound polarity and BBB permeability, with higher permeability for the more polar cathinones. The chemical moieties present in the cathinone had an important impact on the BBB permeability, with lengthening of the α-alkyl chain or functionalization of the aromatic ring with alkyl moieties resulting in lower concentration in telencephalon tissue. Our data suggest that transport of cathinones is a carrier-mediated process, similar to cocaine transport across the BBB.
合成卡西酮是欧洲第二大最常被查获的新型精神活性物质家族。这些化合物与多起中毒事件有关，包括致死案例。尽管已经对卡西酮的药理作用、代谢和药代动力学进行了研究，但关于这些化合物透过血脑屏障（BBB）的通透性的信息却很少。这是了解卡西酮行为和效力的一个重要参数。在这项研究中，对13种选定的卡西酮在腹腔注射剂量为3mg/kg的Sprague-Dawley大鼠的端脑组织中进行了分析。我们的结果揭示了化合物极性与血脑屏障通透性之间的直接关系，极性更强的卡西酮具有更高的通透性。卡西酮中存在的化学基团对血脑屏障通透性有重要影响，α-烷基链的延长或芳环被烷基部分官能化会导致端脑组织中的浓度降低。我们的数据表明，卡西酮的转运是一个载体介导的过程，类似于可卡因透过血脑屏障的转运。
