PMID: 7542758Apr 28, 1995Paper

Enhancement of 7-nitro indazole-induced inhibition of brain nitric oxide synthase by norharmane

Neuroscience Letters
B P ConnopR J Beninger

Abstract

7-Nitro indazole (7-NI) has been used as a selective inhibitor of neuronal nitric oxide synthase (NOS) in vivo. This agent has a short duration of action which may be due to its metabolism. The structure of 7-NI resembles that of tryptophan which can be metabolized by the enzyme indolamine 2,3-dioxygenase (IDO). If 7-NI is also metabolized by this enzyme, then inhibition of IDO should augment the action of 7-NI on brain NOS activity. This possibility was examined by investigating the potential of norharmane, an IDO inhibitor, on the inhibitory effect of 7-NI on NOS catalytic activity (3, 4.5 and 7.5 h post-injection of 7-NI) in five brain regions. Norharmane, which alone did not alter NOS activity, enhanced the action of 7-NI on NOS activity in the cortex (4.5 and 7.5 h), hippocampus (3 h) and substantia nigra (3, 4.5 and 7.5 h) but not in the cerebellum or striatum. This suggests that IDO activity may, at least in part, be responsible for the relatively short duration of 7-NI action.

References

Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·V L DawsonS H Snyder
Jan 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·D S Bredt, S H Snyder
Jul 9, 1991·European Journal of Pharmacology·G A BöhmeJ C Blanchard
Feb 1, 1993·Pain·S T Meller, G F Gebhart

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Citations

Nov 22, 1996·Neuroscience Letters·B E KalischR J Boegman
May 7, 2008·Journal of Agricultural and Food Chemistry·I Rodríguez-MeizosoE Ibáñez

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