EFFECTS OF VARIOUS TETRAHYDROISOQUINOLINE DERIVATIVES ON MITOCHONDRIAL RESPIRATION AND THE ELECTRON-TRANSFER COMPLEXES

We report effect of various tetrahydroisoquinoline derivatives on mito chondrial respiration and the electron transfer complexes. Generally t hese compounds were potent inhibitors of NADH-linked mitochondrial sta te 3 respiration and complex I. Presence of a phenyl group at the C1 p osition or oxidation of N-methylated isoquinones into N-methylisoquino linium ion augmented the potency to inhibit mitochondrial respiration and complex I. Many of these compounds have been identified in human b rains. In view of the mitochondrial and oxidative stress hypothesis, o ur results suggest involvement of these neurotoxins as potential cause s of mitochondrial failure in Parkinson's disease.