Biosynthesis of a parkinsonism-preventing substance, 1-methyl-1,2,3,4-tetrahydroisoquinoline, is inhibited by parkinsonism-inducing compounds in rat brain mitochondrial fraction.

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), an endogenous parkinsonism-preventing substance, is enzymatically synthesized from 2-phenylethylamine (PEA) and pyruvate. We investigated whether exogenous or endogenous parkinsonism-inducing compounds inhibit 1 MeTIQ biosynthesis in a crude enzyme fraction from rat brain. Several parkinsonism-inducing compounds, including tetrahydroisoquinoline derivatives, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1 -methyl-4-phenylpyridinium (MPP+), beta-carboline and haloperidol, inhibited 1MeTIQ biosynthesis. The IC50 value of MPP+ for this enzyme is about 10 microM, lower than that for inhibition of mitochondrial complex I. We propose that the parkinsonism-inducing action of these compounds is at least partly due to inhibition of 1MeTIQ biosynthesis.