Abstract:
Anhydroecgonine Methyl Ester (AEME), also known as methylecgonidine, is the main pyrolysis product of smoking cocaine (cocaine base paste or basuco, crack, or freebase). This review aims to synthesize the available scientific evidence on the toxicokinetic and toxicodynamic effects of AEME. A search of scientific articles published in Science Direct, SCOPUS, and MEDLINE up to May 2024 was conducted. Twenty-four articles, including 13 experimental animal studies, 2 clinical trials, and 3 observational studies, were reviewed. AEME is readily deposited in the alveoli; its absorption improves in combination with cocaine and has a broad tissue distribution. It is metabolized primarily in the liver, with a half-life of approximately one hour, and is mainly excreted through urine. Moreover, AEME acts as a partial agonist of M1 and M3 muscarinic cholinergic receptors, influences dopaminergic system neuroadaptation, increases the production of reactive oxygen species, imbalances the activity of glutathione-associated enzymes, and reduces melatonin levels, affecting its antioxidant regulatory properties. When combined with cocaine, AEME activates the non-apoptotic pathway of caspase-9 and then, the apoptotic pathway via caspase-8, reducing neuronal viability in half the time of cocaine. AEME plays a significant role in cocaine toxicity and AEME itself.
摘要:
脱水秋葵碱甲酯(AEME),也被称为甲基秋黄碱,是吸食可卡因的主要热解产物(可卡因基质糊剂或basuco,裂纹,或freebase)。这篇综述旨在综合有关AEME的毒物动力学和毒物动力学作用的现有科学证据。搜索发表在ScienceDirect上的科学论文,Scopus,并在2024年5月之前进行了MEDLINE。二十四篇,包括13个实验动物研究,2个临床试验,和3项观察性研究,被审查了。AEME容易沉积在肺泡中;它的吸收与可卡因结合会改善,并具有广泛的组织分布。它主要在肝脏代谢,半衰期约为一小时,主要通过尿液排出。此外,AEME作为M1和M3毒蕈碱胆碱能受体的部分激动剂,影响多巴胺能系统的神经适应,增加活性氧的产生,谷胱甘肽相关酶的活性失衡,降低褪黑激素水平,影响其抗氧化调节特性。当与可卡因混合时,AEME激活caspase-9的非凋亡途径,通过caspase-8的凋亡途径,在可卡因的一半时间内降低神经元活力。AEME在可卡因毒性和AEME本身中起着重要作用。