Tetrahydroisoquinoline and its derivatives: the occurrence and the metabolism in the brain, and the effects on catecholamine metabolism
1,2,3,4-Tetrahydroisoquinoline (TIQ) was identified in normal and parkinsonian human brains by gas chromatography-mass spectrometry (GC-MS). In human brain, N-methyl TIQ (NMTIQ) was formed by a N-methyltransferase in the cytosol fraction. The in vivo synthesis of NMTIQ was also confirmed in the brains of marmosets systematically administrated with TIQ. TIQ itself was not oxidized by monoamine oxidase, but NMTIQ was oxidized by both types A and B monoamine oxidase. The oxidative product, N-methylisoquinolinium ion (NMIQ+), inhibited enzymes participating in catecholamine metabolism, such as tyrosine hydroxylase, DOPA decarboxylase and monoamine oxidase. The uptake of NMIQ+ was mediated by the dopamine transport system. These data support our view that TIQ and its derivatives may be candidates of dopaminergic neurotoxin similar to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP).
KeywordsTyrosine Hydroxylase Dopaminergic Neuron Monoamine Oxidase Dopa Decarboxylase Catecholamine Metabolism
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