Department of Neurochemistry, Institute of Pharmacology Polish Academy of Sciences, Smetna Str.12, 31-343, Kraków, Poland,
Neurotox Res. 2014 Jan;25(1):1-12. doi: 10.1007/s12640-013-9402-7. Epub 2013 May 30.
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.
这篇综述概述了 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（1MeTIQ）在大脑中具有高药理潜力和广泛作用谱的内源性物质的影响。1MeTIQ 作为神经保护剂引起了特别的关注，其拮抗众所周知的神经毒素（例如 MPTP；鱼藤酮）产生的行为综合征的能力。因此，本综述重点关注 1MeTIQ 在行为、神经化学和分子研究中的作用机制；TIQ 和 1MeTIQ 对多巴胺代谢的影响；TIQ 和 1MeTIQ 在体外和体内的神经保护特性。最后，将描述 1MeTIQ 在可卡因自我给药大鼠中的抗成瘾特性。研究结果表明，TIQ 及其甲基衍生物 1MeTIQ 参与了中枢神经系统各种神经退行性疾病中独特而复杂的神经保护机制。我们认为，MAO 抑制、自由基清除特性和对抗谷氨酸能系统可能在神经保护中发挥重要作用。此外，这些结果强烈支持这样一种观点，即 1MeTIQ 具有作为一种药物来对抗物质滥用的相当大的潜力，通过减轻渴望。
