[The search for endogenous or exogenous MPTP-like substances]

Abstract

Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in 1983 as a parkinsonian neurotoxin, endogenous or exogenous MPTP-like substances have been extensively investigated. Tetrahydroisoquinoline (TIQ) is a trace amine newly discovered in parkinsonian and control human brains. Like MPTP, TIQ inhibits tyrosine hydroxylase and NADPH ubiquinone oxidoreductase to reduce dopamine and ATP in the nigrostriatal dopaminergic neurons. TIQ produced parkinsonian symptoms after chronic administration in monkeys, which were recovered by L-DOPA. However, TIQ does not cause neuronal cell death at least in young monkeys. If some MPTP-like neurotoxins could be the cause of Parkinson's disease, some other factors such as immunological, neurotrophic, or genetic factors may work together with the putative neurotoxins during the process of aging.