1-Methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine with unexpected mechanism of action: new vistas of therapeutic application.
1-Methyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine with unexpected mechanism of action: new vistas of therapeutic application.
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DOI：
10.1007/s12640-013-9402-7
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发表时间：
2014-01
影响因子：
3.7
通讯作者：
Michaluk J
中科院分区：
文献类型：
--
作者：
Antkiewicz-Michaluk L;Wąsik A;Michaluk J
本文综述了1，2，3，4-四氢异喹啉（TIQ）及其衍生物1-甲基-1，2，3，4-四氢异喹啉（1 MeTIQ）对脑的作用，这些内源性物质具有很高的药理潜力和广泛的作用谱。1 MeTIQ作为一种神经保护剂已经引起了特别的兴趣，其拮抗由众所周知的神经毒素（例如，MPTP;鱼藤酮）。因此，本次审查的重点是在啮齿动物的行为，神经化学和分子研究的作用机制，TIQ和1 MeTIQ对多巴胺代谢的影响，以及TIQ和1 MeTIQ在体外和体内的神经保护特性。最后，抗成瘾特性的1 MeTIQ将在可卡因自我管理的大鼠。研究结果表明TIQ，特别是其甲基衍生物1 MeTIQ在中枢神经系统的各种神经退行性疾病中具有独特而复杂的神经保护机制。我们认为，单胺氧化酶的抑制，自由基清除性能，和拮抗神经递质系统可能在神经保护中发挥重要作用。此外，研究结果强烈支持这样的观点，即1 MeTIQ作为一种药物，通过减弱渴望，具有相当大的潜力，可用于打击药物滥用。
This review outlines the effects of 1,2,3,4-tetrahydroisoquinoline (TIQ) and its derivative, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), endogenous substances imbued with high pharmacological potential and broad spectrum of action in brain. 1MeTIQ has gained special interest as a neuroprotectant, and its ability to antagonize the behavioral syndrome produced by well-known neurotoxins (e.g., MPTP; rotenone). This review is thus focused on mechanisms of action of 1MeTIQ in behavioral, neurochemical, and molecular studies in rodents; also, effects of TIQ and 1MeTIQ on dopamine metabolism; and neuroprotective properties of TIQ and 1MeTIQ in vitro and in vivo. Finally, antiaddictive properties of 1MeTIQ will be described in cocaine self-administered rats. Findings implicate TIQ and especially its methyl derivative 1MeTIQ in unique and complex mechanisms of neuroprotection in various neurodegenerative illnesses of the central nervous system. We believe that MAO inhibition, free radicals scavenging properties, and antagonism to the glutamatergic system may play an essential role in neuroprotection. In addition, the results strongly support the view that 1MeTIQ has a considerable potential as a drug for combating substance abuse, through the attenuation of craving.