NOVEL ENDOGENOUS 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES - UPTAKE BY DOPAMINE TRANSPORTER AND ACTIVITY TO INDUCE PARKINSONISM

Citation
H. Kawai et al., NOVEL ENDOGENOUS 1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES - UPTAKE BY DOPAMINE TRANSPORTER AND ACTIVITY TO INDUCE PARKINSONISM, Journal of neurochemistry, 70(2), 1998, pp. 745-751
Citations number
50
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,Neurosciences
Journal title
ISSN journal
0022-3042
Volume
70
Issue
2
Year of publication
1998
Pages
745 - 751
Database
ISI
SICI code
0022-3042(1998)70:2<745:NE1D-U>2.0.ZU;2-S
Abstract
We designed as candidate metabolites and synthesized two 1-benzyl-1,2, 3,4-tetrahydroisoquinoline derivatives containing a dopamine moiety: 4 '-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4'-DHBnTIQ) and nzyl-6,7-dihydroxy-1,2,3,4-'tetrahydroisoquinoline (6,7DHBnTIQ). Both were detected in mouse brain as endogenous amines by gas chromatograph y/mass spectrometry. 3',4'DHBnTIQ induced parkinsonism in mice when ch ronically administered intraperitoneally, whereas 6,7DHBnTIQ did not d espite the structural similarity of the two compounds. This difference may be related to cellular uptake: In rat striatal synaptosomes, thes e compounds were intracellularly transported by the dopamine transport er with K-m values of 6.14 and 7.82 mu M and V-max values of 214.3 and 112.2 pmol/min/mg of protein, respectively. Thus, endogenous 3',4'DHB nTIQ may be actively transported into dopaminergic neurons and accumul ated there, contributing at least in part to the induction of idiopath ic Parkinson's disease.