Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in Parkinsonian and normal human brains

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1,2,3,4-Tetrahydroisoquinoline (TIQ) and 2-methyl-1,2,3,4-tetrahydroquinoline (2-Me-TQ) were identified for the first time by gas chromatography-mass spectrometry in the parkinsonian and normal human brains. TIQ, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was markedly increased in the parkinsonian brain and could be an endogenous neurotoxin to induce Parkinson's disease.

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    MPTP is a potent, selective dopaminergic neurotoxin and has been widely used for experimental induction of PD (Langston et al., 1983; McNaught et al., 1996a,b; Tariq et al., 2001). TIQ and almost all of its derivatives are thought to participate in development of PD (Niwa et al., 1987; Ohta et al., 1987; Kotake et al., 1995; Abe et al., 2005; Kohta et al., 2010). Recently, we reported that acute intravenous administration of MPTP induces a transient, significant increase in nigral dopaminergic firing and that the effect of TIQ and some of its derivatives (1-MeTIQ, 1-BnTIQ) is weaker than that of MPTP (Chiba et al., 2015).

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    They also reported that its cytotoxicity is reduced by the application of selegiline, one of the therapeutic drugs for the treatment of PD (Hao et al., 1995b), suggesting the presence of PD-causing substances in parkinsonian cerebrospinal fluid. Subsequent examinations have identified various structurally MPTP-like endogenous substances as neurotoxins and it is believed that 1,2,3,4-tetrahydroisoquinoline (TIQ) and its derivatives 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-BnTIQ) and (R)-1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) most likely participate in the pathogenesis of PD (Niwa et al., 1987; Ohta et al., 1987; Kotake et al., 1995; Abe et al., 2005). TIQ derivatives have also been found in the brains of some animal species (Kohno et al., 1986; Kotake et al., 1995; Nakagawa et al., 1996) and either TIQ or 1-BnTIQ can induce parkinsonism in rodents (Tasaki et al., 1991; Kotake et al., 1995).

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    1,2,3,4-Tetrahydroisoquinoline (TIQ) is an endogenous amine that occurs naturally in mammalian organisms, particularly in the brains of humans and rodents [8, 19, 38, 41, 59].

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