Can tetrahydroisoquinoline (TIQ) or N-methyl-TIQ produce parkinsonism?
We have examined the effect of chronic administration of a probable endogenous dopaminergic neurotoxin, tetrahydroisoquinoline (TIQ, 20mg/kg per day, s.c. for up to 104 days), on squirrel monkeys. Chronically administered TIQ produced motor symptoms similar to parkinsonism in squirrel monkeys even after 7 days’ discontinuation of TIQ and the symptoms were alleviated remarkably by levodopa treatment. Biochemical analysis of the brains of TIQ-treated monkeys revealed significant decrease in dopamine (DA) and total biopterin (BP) concentrations, and tyrosine hydroxylase (TH) activity in the substantia nigra. Morphological changes of the substantia nigra of the mice were also analysed. The effect of long-term administration of N-methyl-TIQ on aged monkeys was described.
KeywordsTyrosine Hydroxylase Substantia Nigra Biogenic Amine Squirrel Monkey Motor Disturbance
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