期刊
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
卷 -, 期 -, 页码 -出版社
CANADIAN SCIENCE PUBLISHING
DOI: 10.1139/cjpp-2021-06591
关键词
1; 2; 3; 4-tetrahydroisoquinoline (TIQ); 1-methyl-1; 2; 3; 4-tetrahydroisoquinoline (1-MeTIQ); 1-methyl-4-phenyl-1; 2; 3; 6-tetrahydropyridine (MPTP); dopamine transporter (DAT); Parkinson?s disease
资金
- Ohu University
In this study, the effects of artificially modified 1-MeTIQ derivatives on MPTP-induced PD-like signs in mice were compared. The results showed that loading an N-propargyl group on 1-MeTIQ enhanced its neuroprotective effects, while other functional groups exhibited distinct pharmacological properties. These findings are important for understanding the pathogenesis of PD and developing related therapeutic approaches.
1,2,3,4-tetrahydroisoquinoline (TIQ) is endogenously present in the human brain, and some of its derivatives are thought to contribute to the induction of Parkinson???s disease (PD)-like signs in rodents and primates. In contrast, the endogenous TIQ derivative 1-methyl-TIQ (1-MeTIQ) is reported to be neuroprotective. In the present study, we compared the effects of artificially modified 1-MeTIQ derivatives (loading an N-propyl, N-propenyl, N-propargyl, or N-butynyl group) on 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced PD-like signs in mice. In a behavioral study, MPTP-induced bradykinesia was significantly decreased by all compounds. However, only 1-Me-N-propargyl-TIQ showed an inhibitory effect by blocking the MPTP-induced reduction in striatal dopamine content and the number of nigral tyrosine hydroxylase-positive cells. Western blot analysis showed that 1-Me-N-propargyl-TIQ and 1-Me-N-butynyl-TIQ potently prevented the MPTP-induced decrease in dopamine transporter expression, whereas 1-MeTIQ and 1-Me-N-propyl-TIQ did not. These results suggest that although loading an N-propargyl group on 1-MeTIQ clearly enhanced neuroprotective effects, other N-functional groups showed distinct pharmacological properties characteristic of their functional groups. Thus, the number of bonds and length of the N-functional group may contribute to the observed differences in effect.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据