Effect of Chronic Administration of 1,2,3,4-Tetrahydroisoquinoline and Its Derivatives on the Monkey: Immunohistochemical Study

Abstract

Since 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found to produce symptoms similar to Parkinson’s disease (Langston et al., 1983), toxins with structure similar to MPTP have been hypothesized to result in cell death of mesencephalic dopamine neurons. 1,2,3,4-Tetrahydroisoquinoline (TIQ) has a structure similar to MPTP, and it, and its derivatives exist as endogenous amines in human brain (Ohta et al., 1987; Niwa et al., 1987; Niwa et al., 1989). Toxic properties of TIQ on mitochondria are similar to those of MPP⁺ (the oxidative product of MPTP) (Suzuki et al., 1988). N-methyltetrahydroisoquinoline (NMTIQ) is formed from TIQ by N-methyltransferase (Naoi et al., 1989a). NMTIQ is oxidized by both type A and B monoamine oxidases, and the N-methylisoquinolinium ion (NMIQ⁺), the oxidative product, inhibits activities of enzymes related to catecholamine metabolism (Naoi et al., 1989b). NMTIQ and NMIQ⁺ inhibits complex I activity, similarly to TIQ, and this inhibitory potency of NMIQ⁺ on complex I activity is stronger than that of MPP⁺ (Suzuki et al., 1992). Recently, we administered TIQ and its derivatives (NMTIQ and NMIQ⁺) to monkeys and observed mesencephalic dopamine neurons immunohistochemically. Using light and electron microscopy we found that NMTIQ produces changes in mesencephalic dopamine neurons.