ENHANCEMENT OF 7-NITRO INDAZOLE-INDUCED INHIBITION OF BRAIN NITRIC-OXIDE SYNTHASE BY NORHARMANE

7-Nitro indazole (7-NI) has been used as a selective inhibitor of neur onal nitric oxide synthase (NOS) in vivo. This agent has a short durat ion of action which may be due to its metabolism. The structure of 7-N I 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 br ain NOS activity. This possibility was examined by investigating the p otential 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-N I) in five brain regions. Norharmane, which alone did not alter NOS ac tivity, 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 activit y may, at least in part, be responsible for the relatively short durat ion of 7-NI action.