Time course of inhibition of brain nitric oxide synthase by 7-nitro indazole.
7-Nitro indazole (7-NI) inhibits rat striatal, cerebellar, hippocampal, cerebral cortex and olfactory bulb nitric oxide synthase (NOS) in vitro with IC50 values of 0.68 +/- 0.01 microM, 0.64 +/- 0.03 microM, 1.53 +/- 0.05 microM, 0.93 +/- 0.04 microM and 1.05 +/- 0.02 microM respectively (n = 6). Intraperitoneal (i.p.) or oral administration of 7-NI (30 mg kg-1) to rats inhibited NOS enzyme activity measured ex vivo in all five brain regions (n = 5-6). NOS inhibition (maximal effect, 0.5 h post-injection) was transient with complete recovery at either 4 h (oral administration) or 24 h (i.p. administration). Repeated i.p. injection of 7-NI (30 mg kg-1, every 4 h for 20 h) inhibited NOS enzyme activity at 24 h by 51-61% in all brain regions. The relatively transient NOS inhibitory effect of 7-NI following parenteral administration should be taken into account when using this drug to evaluate the central effects of nitric oxide.
MacKenzie
G M
GM
Neurodegenerative Diseases Research Centre, King's College, London, UK.
Rose
S
S
Bland-Ward
P A
PA
Moore
P K
PK
Jenner
P
P
Marsden
C D
CD
D000284:Administration, Oral; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D066298:In Vitro Techniques; D007191:Indazoles / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D019001:Nitric Oxide Synthase; D051381:Rats; D017208:Rats, Wistar
D007191:Indazoles; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C080122:7-nitroindazole