Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Toxicology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
Crit Rev Toxicol. 2021 Mar;51(3):209-216. doi: 10.1080/10408444.2021.1901258. Epub 2021 Apr 27.
Mefloquine, a potent blood schizontocide, is effective against drug-resistant This property, along with its unique pharmacokinetic profile, makes mefloquine a widely prescribed antimalarial drug. However, several epidemiological studies have raised concerns on the safety of mefloquine as prophylaxis for malaria. Well-documented side-effects of mefloquine include abnormal dreams, insomnia, anxiety, and depressed mood, as well as nausea and dizziness (the last two most frequent effects). The mechanisms that underlie the neurological/psychiatric complications of mefloquine are poorly understood. The aim of this study was to review the literature on the neurotoxic mechanisms of action of mefloquine to better understand its potential toxicity in the central nervous system, highlighting the mechanisms that lead to its psychiatric disorders. Experimental studies on the neurotoxic effects of mefloquine discussed herein include brain transporters of mefloquine, alteration in neurotransmitters, disruption on calcium (Ca) homeostasis and neuroinflammation, generation of oxidative stress response in neurons (involving glutathione, increased F2-isoprostanes, accumulation of cytosolic lipid globules), and alteration of voltage-dependent channels, as well as gap junction intercellular communications. Although several hypotheses have been proposed for the mechanisms that mediate mefloquine-induced brain damage, they are not fully understood, necessitating additional studies in the future.
盐酸甲氟喹是一种强效的血裂殖体杀灭剂，对耐药疟原虫有效。 这种特性，加上其独特的药代动力学特征，使盐酸甲氟喹成为广泛应用的抗疟药物。 然而，几项流行病学研究对盐酸甲氟喹作为疟疾预防药物的安全性提出了担忧。 盐酸甲氟喹有明确记载的副作用包括异常梦境、失眠、焦虑和抑郁，以及恶心和头晕（后两种是最常见的副作用）。 盐酸甲氟喹引起的神经/精神并发症的机制尚不清楚。 本研究旨在综述盐酸甲氟喹神经毒性作用的文献，以更好地了解其在中枢神经系统中的潜在毒性，强调导致其精神障碍的机制。 本文讨论的关于盐酸甲氟喹神经毒性作用的实验研究包括盐酸甲氟喹的脑转运体、神经递质改变、钙（Ca）稳态紊乱和神经炎症、神经元中氧化应激反应的产生（涉及谷胱甘肽、增加的 F2-异前列腺素、细胞溶质脂质球的积累），以及电压依赖性通道的改变以及缝隙连接细胞间通讯。 尽管已经提出了几种用于介导盐酸甲氟喹引起的脑损伤的机制的假说，但这些假说尚未得到充分理解，需要在未来进行更多的研究。
