Neuroprotective effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline on cultured rat mesencephalic neurons in the presence or absence of various neurotoxins

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous brain amine and its content in parkinsonian brain is decreased compared with that in control brain. There is some evidence that 1MeTIQ protects dopaminergic neurons against dysfunction such as that seen in Parkinson's disease. In...

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Bibliographic Details
Published in:Brain research 2005-02, Vol.1033 (2), p.143-150
Main Authors: Kotake, Yaichiro, Taguchi, Ryota, Okuda, Katsuhiro, Sekiya, Yoko, Tasaki, Yoshikazu, Hirobe, Masaaki, Ohta, Shigeru
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Complex I
Dose-Response Relationship, Drug
Female
Male
Medical sciences
Mesencephalon - drug effects
Mesencephalon - metabolism
Mice
Mice, Inbred C57BL
Neurons - drug effects
Neurons - metabolism
Neuropharmacology
Neuroprotective
Neuroprotective agent
Neuroprotective Agents - chemistry
Neuroprotective Agents - pharmacology
Oxidopamine - toxicity
Parkinson's disease
Pharmacology. Drug treatments
Pregnancy
Primary mesencephalic culture
Rats
Rats, Wistar
Rotenone - toxicity
Tetrahydroisoquinoline
Tetrahydroisoquinolines - chemistry
Tetrahydroisoquinolines - pharmacology
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Summary:1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous brain amine and its content in parkinsonian brain is decreased compared with that in control brain. There is some evidence that 1MeTIQ protects dopaminergic neurons against dysfunction such as that seen in Parkinson's disease. In this study, we examined the neuroprotective effect of 1MeTIQ against four dopaminergic neurotoxins, 1-methyl-4-phenylpyridinuim ion, 6-hydroxydopamine, rotenone, and l-benzyl-1,2,3,4-tetrahydroisoquinoline, in cultured rat mesencephalic neurons. 1MeTIQ exerted neuroprotective action against all these toxins. Furthermore, ( R)-1MeTIQ was neuroprotective, while ( S)-1MeTIQ had little effect, indicating that the effect is stereoselective. The protective action of 1MeTIQ was most effective in mesencephalic neurons, especially in tyrosine hydroxylase-positive neurons. 1MeTIQ showed no affinity for dopamine receptors and did not influence the inhibition of mitochondrial respiratory complex I by rotenone, 1-methyl-4-phenylpyridinuim ion, or 1-benzyl-1,2,3,4-tetrahydroisoquinoline. These results raise the possibility that 1MeTIQ indirectly acts as an anti-oxidant such as the induction of anti-oxidative enzymes, because all these four neurotoxins can burden oxidative stress in common. This is the first report to confirm a protective effect of 1MeTIQ at the cultured neuron level, and it may have potential as a lead compound for the development of new agents to treat Parkinson's disease.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2004.11.019