Altun Beril, Çok İsmet
Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey.
Turk J Pharm Sci. 2020 Apr;17(2):235-241. doi: 10.4274/tjps.galenos.2018.40820. Epub 2020 Apr 24.
Synthetic cathinones are new designer drugs that possess hallucinogenic and psychostimulant properties, and are designed to mimic the effects of illegal substances such as cocaine, amphetamines, and 3.4-methylenedioxymethamphetamine (ecstasy) and to produce rewarding effects, circumventing existing laws and penalties. Synthetic cathinones, also referred to as 'bath salts', have become popular particularly among young people since the mid-2000s. Similar to other psychomotor stimulants, synthetic cathinones have the potential to increase monoamine concentration in the synaptic cleft by targeting the plasma membrane transporters of dopamine, norepinephrine, and serotonin. Because of their structural similarities to amphetamines, it has been suggested that synthetic cathinones may have a neurotoxicity profile similar to that of their amphetamine congeners. Therefore, it has been hypothesized that synthetic cathinones may induce neurotoxicity on monoamine nerve endings in the striatum, hippocampus, and cortex. To date, with regard to synthetic cathinone neurotoxicity, parameters such as monoamine depletion, biosynthetic enzyme inhibition, cytotoxicity, generation of reactive oxygen species, pro-oxidation status, and the ability to induce neuroinflammation were investigated in both and experimental studies. Compared with amphetamines, synthetic cathinones appear to have more moderate effects than their amphetamine congeners in terms of neurotoxic effects. However, many synthetic cathinone users take these substances simultaneously with other substances such as benzodiazepines, amphetamines, ecstasy, tetrahydrocannabinol, and ethanol and this abuse can modify their neurotoxic effects. Hence, it is important to understand the underlying mechanism of early neurotoxic effects in case of polysubstance use. In this review, we aimed to present up-to-date information on the abuse potential of synthetic cathinones, their legal status, mechanism of action, and particularly their neurotoxic effects.
合成卡西酮是一类新型的设计药物,具有致幻和精神兴奋特性,旨在模拟可卡因、安非他命和3,4-亚甲基二氧甲基苯丙胺(摇头丸)等非法物质的效果,并产生奖赏效应,从而规避现行法律和处罚。合成卡西酮,也被称为“浴盐”,自21世纪中期以来在年轻人中尤其流行。与其他精神运动兴奋剂类似,合成卡西酮有可能通过作用于多巴胺、去甲肾上腺素和5-羟色胺的质膜转运体来增加突触间隙中的单胺浓度。由于它们在结构上与安非他命相似,有人提出合成卡西酮可能具有与其安非他命同系物相似的神经毒性特征。因此,有人推测合成卡西酮可能会对纹状体、海马体和皮质中的单胺神经末梢产生神经毒性。迄今为止,关于合成卡西酮神经毒性,在体内和体外实验研究中都对诸如单胺耗竭、生物合成酶抑制、细胞毒性、活性氧生成、促氧化状态以及诱导神经炎症的能力等参数进行了研究。与安非他命相比,合成卡西酮在神经毒性作用方面似乎比其安非他命同系物的作用更为温和。然而,许多合成卡西酮使用者会同时将这些物质与其他物质如苯二氮䓬类、安非他命、摇头丸、四氢大麻酚和乙醇一起服用,这种滥用情况会改变它们的神经毒性作用。因此,了解多药滥用情况下早期神经毒性作用的潜在机制很重要。在这篇综述中,我们旨在呈现关于合成卡西酮的滥用潜力、法律地位、作用机制,尤其是其神经毒性作用的最新信息。