Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester
Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, N-G-nitro-L-arginine methyl ester
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DOI：
10.1016/0024-3205(93)90472-f
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发表时间：
1993-01-01
期刊：
影响因子：
6.1
通讯作者：
Cicero, Theodore J.
中科院分区：
文献类型：
--
作者：
Adams, Michael L.;Kalicki, Joelle M.;Cicero, Theodore J.
在成年雄性大鼠皮下植入一粒吗啡（75 mg）3天，然后用纳洛酮催促戒断（0.5 mg/kg），验证了吗啡-一氧化氮（NO）还原酶-NO系统介导吗啡戒断综合征的假设。在纳洛酮诱导的戒断前不久注射NO合酶抑制剂N-G-硝基-L-精氨酸甲酯（NAME，100 mg/kg皮下注射）可显著抑制戒断体征25- 80%。在吗啡身体依赖的发展过程中和纳洛酮催促戒断过程中，通过皮下渗透泵持续输注NAME也抑制了吗啡戒断体征。此外，硝酸异山梨酯，一氧化氮供体，治疗诱导了一个准吗啡戒断综合征（QMAS），显着抑制植入吗啡丸硝酸异山梨酯治疗前3天。这些结果表明，NO介导的吗啡戒断综合征的表达的一部分。
The hypothesis that an arginine-nitric oxide (NO) synthase-NO system mediates the morphine abstinence syndrome was tested in adult male rats implanted subcutaneously for 3 days with one morphine (75 mg) pellet followed by naloxone-precipitated withdrawal (0.5 mg/kg). Injection with a NO synthase inhibitor, N-G-nitro-L-arginine methyl ester (NAME, 100 mg/kg subcutaneous), shortly before naloxone-induced withdrawal significantly inhibited abstinence signs by 25-80%. Continuous infusion of NAME via subcutaneous osmotic pumps during the development of morphine physical dependence and during naloxone-precipitated withdrawal also inhibited morphine abstinence signs. In addition, treatment with isosorbide dinitrate, a NO donor, induced a quasi morphine-abstinence syndrome (QMAS) that was significantly suppressed by implantation of a morphine pellet 3 days before isosorbide dinitrate treatment. These results indicate that NO mediates part of the expression of the morphine abstinence syndrome.