Endogenous MPTP-Like Amines in the Brain: Isoquinolines
The discovery of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as a parkinsonism-producing neurotoxin (Davis et al., 1979; Langston et al., 1983) has greatly contributed to the pathogenesis of Parkinson’s disease. Efforts have been made to find MPTP-like neurotoxins in the brain of parkinsonian patients. MPTP is a precursor neurotoxin, and the oxidized form, by monoamine oxidase type B, N-methyl-4-phenylpyridinium ion (MPP+), is the active neurotoxin (Chiba et al., 1984). It is assumed, therefore, that if any hypothetical MPTP-like neurotoxins exist in the parkinsonian brain they might be oxidized by monoamine oxidase to active neurotoxins.
KeywordsTyrosine Hydroxylase Monoamine Oxidase Normal Human Brain Nigrostriatal Dopamine Nigrostriatal Dopaminergic Neuron
Unable to display preview. Download preview PDF.
- Makino Y, Tasaki Y, Ohta S, Hirobe M (1990): Confirmation of the enantiomers of 1-methyl-1,2,3,4-tetrahydroisoquinoline in the mouse brain and foods applying gas chromatography/mass spectrometry with negative ion chemical ionization. Biomed Environ Mass Spectrom 19:415–419PubMedCrossRefGoogle Scholar
- Michel PP, Dandapani BK, Sanchez-Ramos, J, Efange S, Pressman BC, Hefti F (1989): Toxic effects of potential environmental neurotoxins related to 1-methyl-4-phenylpyridium on cultured rat dopaminergic neurons. J Pharmacol Exp Therap 248:842–850Google Scholar
- Niijima K, Araki M, Ogawa M, Suzuki K, Mizuno Y, Nagatsu I, Kimura H, Yoshida M, Nagatsu T (1991): N-Methylisoquinolinium ion (NMIQ+) destroys cultured mesencephalic dopamine neurons. Biog Amines 8:61–67Google Scholar
- Niwa T, Takeda N, Yoshizumi H, Tatematsu A, Yoshida M, Dostert P, Naoi M, Nagatsu T (1991): Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoqui-noline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, novel endogenous amines, in parkinsonian and normal human brains. Biochem Biophys Res Commun 177:603–609PubMedCrossRefGoogle Scholar
- Niwa T, Maruyama W, Nakahara D, Takeda N, Yoshizumi H, Tatematsu A, Takahashi A, Dostert P, Naoi M, Nagatsu T (1992): Endogenous synthesis of N-methylsalsolinol, an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, in rat brain during in vivo microdialysis with salsolinol as demonstrated by gas chromatography-mass spectrometry. J Chromatogr 578:109–115PubMedCrossRefGoogle Scholar
- Ogawa M, Araki M, Nagatsu I, Nagatsu T, Yoshida M (1989): The effect of 1,2,3,4-tetrahydroisoquinoline (TIQ) on mesencephalic dopaminergic neurons inC57BL/6J mice: immunohistochemical studies — tyrosine hydroxylase. Biog Amines 6:427–436Google Scholar
- Ohta S, Kohno M, Makino Y, Tachikawa O, Hirobe M (1987): Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline are present in the human brain: relation to Parkinson’s disease. Biomed Res 8:453–456Google Scholar
- Strolin-Benedetti M, Dostert P (1992): Monoamine oxidase: from physiology and pathophysiology to the design and clinical application to reversible inhibitors. In: Advances in Drug Research, Vol. 23, Testa B, ed., pp. 65–125. San Diego: Academic PressGoogle Scholar