Four inhibitors of nitric oxide synthase (NOS), administered as acute pretreatments, attenuated several signs of naloxone-precipitated opioid withdrawal in morphine-dependent rats. Profiles of these drugs for inhibiting the expression of withdrawal were similar to that of clonidine, a drug used clinically to treat opioid withdrawal. The nonselective NOS inhibitors, NG-nitro-L-arginine and NG-nitro-L-argtnine methyl ester, and N(5)-(l-iminoethyl)-L-ornithine, a selective inhibitor of endothelial NOS, increased blood pressure in awake, morphine-naive and morphine-dependent rats not undergoing withdrawal. 7-Nitroindazole, a selective inhibitor of neuronal NOS, did not elevate blood pressure. Insofar as hypertension is a component of opioid withdrawal in humans, the ability of 7-nitroindazole to attenuate morphine withdrawal in rats without eliciting a vasopressor response suggests that 7-nitroindazole may have human therapeutic potential. Research directions for the continued development of 7-nitroindazole as a therapeutic modality are discussed with respect to issues of physical dependence, tolerance, and safety. © 1995 American College of Neuropsychopharmacology.
Vaupel, D. B., Kimes, A. S., & London, E. D. (1995). Nitric oxide synthase inhibitors preclinical studies of potential use for treatment of opioid withdrawal. Neuropsychopharmacology. https://doi.org/10.1016/0893-133X(95)00138-4