Beta-carboline analogues of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP): endogenous factors underlying idiopathic parkinsonism?

A remarkable structural similarity exists between the parkinsonian neurotoxin, N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), and 2-[N]-methyl-tetrahydro-beta-carboline (2M-THBC), a tryptamine-derived alkaloid which can be biosynthesized in brain. To explore whether the beta-carboline also has neurotoxic effects, owl monkeys were treated daily with MPTP or 2M-THBC. Acute behavioral similarities were seen, but 2M-THBC did not induce persistent parkinsonism, nor did it cause apparent loss of nigral cells. However, 2M-THBC resembled MPTP in reducing 3,4-dihydroxyphenylacetic acid levels in caudate and in altering levels of serotonin and 5-hydroxyindoleacetic acid in substantia nigra. These limited similarities should be considered in the light of relationships between neurotoxicity, MPTP versus 2M-THBC oxidation, and the chronicity of human Parkinson's disease. We suggest that N-methylated beta-carboline species, possibly accumulating during stress and aging, could well be causative factors in parkinsonism.