[A new procedure for the determination of N-methylisoquinolinium ion, and its application]

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of dopaminergic nigrostriatal pathways in humans and monkeys resulting in a syndrome similar to idiopathic parkinsonism. MPTP is first metabolized to 1-methyl-4-phenylpyridine (MPP+), a primary neurotoxin, by monoamine oxidase B (MAO-B) and then taken up into dopaminergic neurons through the dopamine reuptake system. Although the molecular basis of this toxicity in destroying the nigro-striatal system has not been well established, the discovery of MPTP has led to extensive studies trying to find substances that produce parkinsonism. Tetrahydroisoquinoline has been presumed to be as an endogenous toxic substance that may produce parkinsonism. Furthermore, the presence of tetrahydroisoquinoline as a novel endogenous amine in the rat and human brains has recently been documented. In this paper, the author describes a new procedure for quantitation of N-methylisoquinolinium ion (NMIQ+), the oxidative analog of N-methylated tetrahydroisoquinoline, by use of its natural fluorescence and high-performance liquid chromatography. The separation of NMIQ+ was carried out by ion exchange chromatography on a column of weakly acidic ion exchanger with an hydrophilic matrix (Asahipak ES-502C) and by gel filtration chromatography on a column of hydrophilic polymer gels (Asahipak-320H). The method was simple and sensitive enough to measure less than 50 fmol of NMIQ+. The uptake of NMIQ+ by rat striatal slices was found by applying this method to the sliced tissue. The uptake was shown to be inhibited by nomifensine, a selective inhibitor of dopamine uptake. The result suggests that NMIQ+ as well as MPP+ is taken up into dopaminergic neurons by the dopamine uptake system.