7-Nitro indazole, an inhibitor of nitric oxide synthase, exhibits anti-nociceptive activity in the mouse without increasing blood pressure

Br J Pharmacol. 1993 Feb;108(2):296-7. doi: 10.1111/j.1476-5381.1993.tb12798.x.

Abstract

7-Nitro indazole (7-NI) inhibits mouse cerebellar nitric oxide synthase (NOS) in vitro with an IC50 of 0.47 microM. Following i.p. administration in mice, 7-NI (10-50 mg kg-1) produces dose-related anti-nociception as evidenced by an inhibition of late phase (15-30 min) but not early phase (0-5 min) hindpaw licking time following subplantar injection of formalin (10 microliters, 5% v/v). The ED50 for this effect was 26 mg kg-1 (equivalent to 159.5 mumol kg-1). Similar i.p. administration of 7-NI (20 and 80 mg kg-1) in urethane-anaesthetized mice failed to increase MAP. Thus, 7-NI is a novel inhibitor of NOS which exhibits selectivity for the brain enzyme. Accordingly, 7-NI may be a useful starting point for the development of selective, centrally acting NOS inhibitors devoid of cardiovascular side effects and as a tool to study the central pharmacological effects of nitric oxide (NO).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Analgesics*
  • Animals
  • Blood Pressure / drug effects*
  • Cerebellum / drug effects
  • Cerebellum / enzymology
  • Formaldehyde / antagonists & inhibitors
  • In Vitro Techniques
  • Indazoles / pharmacology*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Nitric Oxide Synthase
  • Sensitivity and Specificity

Substances

  • Analgesics
  • Indazoles
  • Formaldehyde
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • 7-nitroindazole