Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP |
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Authors: | Raymond G. Booth Neal Castagnoli Jr. Hans Rollema |
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Affiliation: | Department of Pharmaceutical Chemistry, Division of Toxicology, University of California, San Francisco CA 94143, U.S.A. |
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Abstract: | The in vivo dopaminergic neurotoxicity of a series of quinoline and isoquinoline derivatives was assessed in rats using an intrastriatal microdialysis technique that measures the release of dopamine. The N-methyl quaternary salts of these two heterocyclic aromatic systems displayed about 10% of the potency of MPP+ in this assay. Furthermore, tetrahydroisoquinoline, which has been reported to be present in human brain, and N-methyltetrahydroisoquinoline were found to be MAO-B substrates, being oxidized at about 3% the rate of MPTP. Thus, although tetrahydroisoquinoline and N-methyltetrahydroisoquinoline are not neurotoxic, it is conceivable that the chronic endogenous formation of quaternary species could cause neuronal lesions that contribute to the etiology of idiopathic Parkinson's disease. |
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Keywords: | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-Methyl-4-phenylpyridinum Tetrahydroisoquinoline Quinoline Isoquinoline Endogenous neurotoxin Microdialysis |
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