Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine].
Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine].
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血清素神经毒素 2-(甲氨基)-1-[3,4-(亚甲二氧基)苯基]丙烷 [(亚甲二氧基)甲基苯丙胺] 的假定代谢物的合成和神经毒理学评估。
DOI：
10.1021/tx00025a015
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发表时间：
1992
影响因子：
4.1
通讯作者：
Martello,M
中科院分区：
文献类型：
--
作者：
Zhao,ZY;CastagnoliJr,N;Ricaurte,GA;Steele,T;Martello,M
理论考虑和最近的实验数据促使人们研究了6-羟基多巴胺类似物2-(甲氨基)-L-(2，4，5-三羟基苯基)丙烷(5)及其可能的前体L-[2-羟基-4，5-(亚甲二氧基)苯基]-2-(甲氨基)丙烷(4)，它们是5-羟色胺能神经毒素MDMA的潜在代谢物。全身、脑室和实质内(纹状体和皮质内)给药4导致在已建立的神经毒素导致显著生物胺耗竭的条件下，大鼠的海马体或皮质5-羟色胺或纹状体多巴胺水平没有检测到变化。相比之下，脑实质内注射5-羟色胺会导致多巴胺和5-羟色胺的严重消耗，前者的消耗比后者更严重。虽然这些数据不是决定性的，但这些数据表明5在MDMA的神经毒性作用的中介中可能发挥了作用。
Theoretical considerations and recent experimental datahave prompted an investigation of the neurotoxicologifcal properties of the 6-hydroxydopamine analogue 2-(methylamino)-l-(2, 4, 5-trihydroxyphenyl) propane (5) and its possible precursor l-[2-hydroxy-4, 5-(methylenedioxy) phenyl]-2-(methylamino) propane (4), potential metabolites of the serotonergic neurotoxin MDMA. Systemic, intracerebroventricular, and intraparenchymal (intrastriatal and intracortical) administration of 4 led to no detectable alterations of hippocampal or cortical serotonin or striatal dopamine levels in the rat under conditions that caused significant biogenic amine depletions by established neurotoxins. By contrast, intraparenchymal administration of 5 caused profound depletions of dopamine and serotonin, with the former being more severely depleted than the latter. Although not conclusive, these data suggest a possible role for 5 in the mediation of MDMA’s neurotoxic actions.