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.
Collins
M A
MA
Neafsey
E J
EJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D001029:Aotus trivirgatus; D002243:Carbolines / Q000633:toxicity*; D002421:Caudate Nucleus / Q000032:analysis; D004298:Dopamine / Q000032:analysis; D006719:Homovanillic Acid / Q000032:analysis; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D007211:Indoles / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology*; D010302:Parkinson Disease, Secondary / Q000209:etiology; D011725:Pyridines / Q000633:toxicity*; D012701:Serotonin / Q000032:analysis; D013378:Substantia Nigra / Q000032:analysis
D002243:Carbolines; D007211:Indoles; D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; C009777:2-methyltryptoline; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid