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).