7-Nitroindazole and its rapidly emerging role in opioid pain management and withdrawal

Correspondence: Shailendra Kapoor 2300 E Cary Street, Richmond, VA 23223, USA Email [email protected] To the editor I read with great interest the paper by Jin et al in a recent issue of your journal. The article is highly thought-provoking. Interestingly, the past few years have also seen the emergence of nitric oxide synthetase inhibitors, especially 7-nitroindazole, as novel new agents with significant benefits in opioid pain management and withdrawal. For instance, 7-nitroindazole attenuates the development of tolerance to the antinociceptive activity of kappa and mu opioid receptors. Similarly, 7-nitroindazole blocks the neurotoxicity secondary to ketamine in animal models. This may very well play a significant role in protecting the human brain from the toxicity of ketamine, especially in the pediatric population. 7-Nitroindazole also has a negative impact on morphine dependency. Tian et al have shown that 7-nitroindazole decreases physical dependence on opioid agonist/antagonist agents such as butorphanol. Medvedev et al have recently shown that administration of 7-nitroindazole also decreases symptoms of opioid withdrawal, such as tremors and diarrhea. The clinical benefit of 7-nitroindazole in individuals with opioid withdrawal is that it does not cause hypertension, unlike other nitric oxide synthase inhibitors, such as L-NG-nitroarginine methyl esters. 7-Nitroindazole may also have other benefits. For instance, 7-nitroindazole injection into the bronchial vasculature decreases pulmonary changes such as edema secondary to hypoxic trauma. The examples cited here clearly illustrate the beneficial effects of 7-nitroindazole and the need for further large-scale studies to elaborate fully its beneficial effects in pain management.