Relationship between TIQs and Parkinson’s disease
1,2,3,4-Tetrahydroisoquinoline (TIQ) has been assumed to be one of the endogenous substances inducing Parkinson’s disease because of its structural similarity to 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
Actually TIQ and its related compound, 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) were coexistent as endogenous amines in rat brain and human brain. lMeTIQ content was markedly reduced in the parkinsonian brain particularly in the frontal lobe. The 1MeTIQ content also decreased with aging.
TIQs were present in foods, such as wine, cocoa, cheese, milk, egg and banana. In addition, TIQs could penetrate the blood-brain barrier, and hence TIQ from foods may accumulate in the brain over long periods.
Metabolism of TIQ was investigated in connection with metabolism of debrisoquine which is a common marker for the metabolism in human. The main metabolite of TIQ was 4-hydroxy-TIQ. Urinary excretion of 4OH-TIQ was significantly reduced in female DA rat, an animal model of a poor debrisoquine metabolizer. The female DA rat also showed significantly higher brain accumulation of TIQ. These results suggest that the metabolic detoxication process is depressed and TIQ accumulation in the brain is enhanced in a poor debrisoquine metabolizer, which may be one possible explanation for poor debrisoquine metabolizers being susceptible to Parkinson’s disease.
KeywordsParkinsonian Brain Brain Accumulation Endogenous Amine Cycad Seed Chronic Parkinsonism
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