Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Pharmacol Biochem Behav. 2011 Oct;99(4):671-5. doi: 10.1016/j.pbb.2011.06.025. Epub 2011 Jun 29.
On the basis of efficacy, opioid antagonists are classified as inverse opioid agonists (e.g. naltrexone) or neutral opioid antagonists (e.g. 6β-naltrexol). This study examined the interaction between naltrexone and 6β-naltrexol in the precipitated opioid withdrawal syndrome in morphine dependent mice. Furthermore, the possible contribution of constitutive opioid receptor activity to precipitated withdrawal was evaluated using increasing levels of morphine dependence. In the first experiment, low doses of 6β-naltrexol antagonized naltrexone precipitated withdrawal while high doses acted additively. All doses of naltrexone increased 6β-naltrexol's potency to precipitate withdrawal. The next experiment examined changes in antagonist potency to precipitate withdrawal with increasing morphine dependence. Mice were exposed to morphine for 1-6 days and then withdrawal was precipitated. Naltrexone was more potent than 6β-naltrexol at all the time points. The ED(50) of both drugs decreased at the same rate suggesting that increased dependence produced no change in constitutive opioid receptor activity. Taken together these results indicate that the functional efficacy of 6β-naltrexol is dose-dependent and that constitutive opioid receptor activity did not change as opioid dependence increased from 1 to 6 days.
根据疗效，阿片受体拮抗剂可分为反向阿片激动剂（如纳曲酮）或中性阿片受体拮抗剂（如 6β-纳曲醇）。本研究考察了纳曲酮和 6β-纳曲醇在吗啡依赖小鼠阿片戒断综合征中的相互作用。此外，还使用不同程度的吗啡依赖来评估组成型阿片受体活性对戒断的可能贡献。在第一项实验中，低剂量的 6β-纳曲醇拮抗纳曲酮引起的戒断，而高剂量则起相加作用。纳曲酮的所有剂量都增加了 6β-纳曲醇引起戒断的效力。第二项实验研究了随着吗啡依赖程度的增加，拮抗剂引起戒断的效力变化。将小鼠暴露于吗啡 1-6 天，然后诱发戒断。纳曲酮在所有时间点均比 6β-纳曲醇更有效。两种药物的 ED（50）以相同的速度降低，这表明增加的依赖并没有改变组成型阿片受体活性。综上所述，这些结果表明 6β-纳曲醇的功能效力是剂量依赖性的，而且随着从 1 天到 6 天吗啡依赖的增加，组成型阿片受体活性没有变化。
