Vaupel D B, Kimes A S, London E D
Neuroimaging and Drug Action Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD USA.
Neuropsychopharmacology. 1995 Dec;13(4):315-22. doi: 10.1016/0893-133X(95)00138-4.
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-arginine methyl ester, and N(5)-(1-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.
四种一氧化氮合酶（NOS）抑制剂作为急性预处理药物，可减轻吗啡依赖大鼠中纳洛酮诱发的阿片类药物戒断的几种症状。这些药物抑制戒断症状表达的情况与可乐定相似，可乐定是临床上用于治疗阿片类药物戒断的药物。非选择性NOS抑制剂NG-硝基-L-精氨酸和NG-硝基-L-精氨酸甲酯，以及内皮型NOS的选择性抑制剂N（5）-（1-亚氨基乙基）-L-鸟氨酸，可使清醒的、未接触过吗啡的和未处于戒断状态的吗啡依赖大鼠血压升高。神经元型NOS的选择性抑制剂7-硝基吲唑不会升高血压。鉴于高血压是人类阿片类药物戒断的一个组成部分，7-硝基吲唑在不引发血管升压反应的情况下减轻大鼠吗啡戒断症状的能力表明，7-硝基吲唑可能具有人类治疗潜力。关于身体依赖性、耐受性和安全性问题，讨论了将7-硝基吲唑持续开发为一种治疗方式的研究方向。
