Novel endogenous 1,2,3,4-tetrahydroisoquinoline derivatives: uptake by dopamine transporter and activity to induce parkinsonism.

Abstract:

:We designed as candidate metabolites and synthesized two 1-benzyl-1,2,3,4-tetrahydroisoquinoline derivatives containing a dopamine moiety: 1-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline (3',4'DHBnTIQ) and 1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (6,7DHBnTIQ). Both were detected in mouse brain as endogenous amines by gas chromatography/mass spectrometry. 3',4'DHBnTIQ induced parkinsonism in mice when chronically administered intraperitoneally, whereas 6,7DHBnTIQ did not despite the structural similarity of the two compounds. This difference may be related to cellular uptake: In rat striatal synaptosomes, these compounds were intracellularly transported by the dopamine transporter with Km values of 6.14 and 7.82 microM and Vmax values of 214.3 and 112.2 pmol/min/mg of protein, respectively. Thus, endogenous 3',4'DHBnTIQ may be actively transported into dopaminergic neurons and accumulated there, contributing at least in part to the induction of idiopathic Parkinson's disease.

journal_name

J Neurochem

authors

Kawai H,Makino Y,Hirobe M,Ohta S

doi

10.1046/j.1471-4159.1998.70020745.x

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

745-51

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

70

pub_type

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