Abstract
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ), unlike several other tetrahydroisoquinolines, displays neuroprotective properties. To elucidate this action we compared the effects of 1MeTIQ with 1,2,3,4-tetrahydroisoquinoline (TIQ), a compound sharing many activities with 1MeTIQ (e.g., reducing free radicals formed during dopamine catabolism) but offering no clear neuroprotection. We found that the compounds similarly inhibit free radical generation in an abiotic system, as well as indices of neurotoxicity, caspase-3 activity, and lactate dehydrogenase release induced by glutamate in mouse embryonic primary cell cultures. 1MeTIQ also prevents the glutamate-induced cell death and 45Ca2+ influx, whereas TIQ did not. In vivo microdialysis study has shown that 1MeTIQ prevents kainate-induced release of excitatory amino acids from the rat frontal cortex. Additionally, 1MeTIQ protects against rotenone-induced mortality, oxidative stress as well as dopaminergic neurodegeneration in the extrapyramidal structures produced by intracerebral injection of rotenone. The results suggest that 1MeTIQ offers a unique and complex mechanism of neuroprotection in which free radicals scavenging properties and inhibition of glutamate-induced excitotoxicity may play a very important role, and indicates the potential of 1MeTIQ as a therapeutic agent in various neurodegenerative illnesses of the central nervous system.
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The authors thank Polish Committee of Scientific Research (project N N401 004836) and the statutory funds of the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland for financial support.
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Vetulani, J., Antkiewicz-Michaluk, L. (2012). 1-Methyl-1,2,3,4-Tetrahydroisoquinoline: A Potent Neuroprotecting Agent. In: Antkiewicz-Michaluk, L., Rommelspacher, H. (eds) Isoquinolines And Beta-Carbolines As Neurotoxins And Neuroprotectants. Current Topics in Neurotoxicity, vol 1. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1542-8_3
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