The endogenous amine 1-methyl-1,2,3,4-tetrahydroisoquinoline prevents the inhibition of complex I of the respiratory chain produced by MPP+

The endogenous monoamine 1-methyl-1,2,3,4-tetrahydroisoquinoline has been s hown to prevent the neurotoxic effect of MPP+ and other endogenous neurotox ins, which produce a parkinsonian-like syndrome in humans. We have tested i ts potential protective effect in vivo by measuring the protection of 1-met hyl-1,2,3,4-tetrahydroisoquinoline in the neurotoxicity elicited by MPP+ in rat striatum by tyrosine hydroxylase immunocytochemistry. Because we know that cellular damage caused by MPP+ is primarily the result of mitochondria l respiratory inhibition at the complex I lever, we have extended the study further to understand this protective mechanism. We found that the inhibit ory effect on the mitochondrial respiration rate induced by MPP+ in isolate d rat liver mitochondria and striatal synaptosomes was prevented by additio n of 1-methyl-1,2,3,4-tetrahydroisoquinoline. This compound has no antioxid ant capacity; therefore, this property is not involved in its protective ef fect. Thus, we postulate that the preventive effect that 1-methyl-1,2,3,4-t etrahydroisoquinoline has on mitochondrial inhibition for MPP+ could be due to a "shielding effect," protecting the energetic machinery, thus preventi ng energetic failure. These results suggest that this endogenous amine may protect against the effect of several parkinsonism-inducing compounds that are associated with progressive impairment of the mitochondrial function.