Abstract
Here we report that bis(7)-tacrine, a novel acetylcholinesterase inhibitor, exerts neuroprotective effects by inhibition of nitric oxide synthase. In cortical neurons at 12 days in vitro, bis(7)-tacrine concentration-dependently reduced cell death induced by glutamate, beta-amyloid and L-arginine, but not by nitric sodium nitroprusside. N-monomethyl-L-arginine, a nitric oxide synthase inhibitor, also prevented the former three types but not the last type of the cytotoxicity; however, nitric oxide scavengers blocked all of these insults, indicating that nitric oxide mediated these neuronal injuries. Furthermore, with nitric oxide synthase activity assays, it was found that bis(7)-tacrine not only suppressed the activation of nitric oxide synthase caused by glutamate in cortical neurons, but also directly inhibited the activity of nitric oxide synthase in vitro.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Benzimidazoles
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Cell Death / drug effects
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects
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Fluoresceins
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Fluorescent Dyes
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Glutamic Acid / pharmacology
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Neurons / drug effects
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Neuroprotective Agents*
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Neurotoxins / antagonists & inhibitors
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Nitric Oxide / physiology
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Nitric Oxide Synthase Type I / antagonists & inhibitors*
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Nitric Oxide Synthase Type I / metabolism
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Rats
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Rats, Sprague-Dawley
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Tacrine / analogs & derivatives*
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Tacrine / pharmacology
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omega-N-Methylarginine / pharmacology
Substances
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1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
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Benzimidazoles
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Fluoresceins
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Fluorescent Dyes
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Neuroprotective Agents
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Neurotoxins
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omega-N-Methylarginine
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Nitric Oxide
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Glutamic Acid
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Tacrine
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Nitric Oxide Synthase Type I
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bisbenzimide ethoxide trihydrochloride
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diacetylfluorescein