Neuroprotection via inhibition of nitric oxide synthase by bis(7)-tacrine.

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.

• Authors: Wenming Li, Nelson T K Lee, Hongjun Fu, Kelvin K W Kan, Yuanping Pang, Mingtao Li, Karl W K Tsim, Xiaoyuan Li, Yifan Han
• Journal: Neuroreport (Neuroreport) Vol. 17 Issue 5 Pg. 471-4 (Apr 03 2006) ISSN: 0959-4965 [Print] England
• PMID: 16543809 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine
• Benzimidazoles
• Fluoresceins
• Fluorescent Dyes
• Neuroprotective Agents
• Neurotoxins
• omega-N-Methylarginine
• Nitric Oxide
• Glutamic Acid
• Tacrine
• Nitric Oxide Synthase Type I
• bisbenzimide ethoxide trihydrochloride
• diacetylfluorescein

Topics

• Animals
• Benzimidazoles
• Cell Death (drug effects)
• Cells, Cultured
• Cerebral Cortex (cytology, drug effects)
• Fluoresceins
• Fluorescent Dyes
• Glutamic Acid (pharmacology)
• Neurons (drug effects)
• Neuroprotective Agents
• Neurotoxins (antagonists & inhibitors)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type I (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Tacrine (analogs & derivatives, pharmacology)
• omega-N-Methylarginine (pharmacology)