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

Abstract

7‐Nitro indazole (7‐NI) inhibits mouse cerebellar nitric oxide synthase (NOS) in vitro with an IC50 of 0.47 μm. 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 μl, 5% v/v). The ED50 for this effect was 26 mg kg−1 (equivalent to 159.5 μmol 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). 1993 British Pharmacological Society