In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 100, No. 7 ( 2022-07-01), p. 594-611
Abstract:
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-1,2,3,6-tetrahydropyridine (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.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
DOI:
10.1139/cjpp-2021-0659
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2022
detail.hit.zdb_id:
2004356-9
Permalink