Walker J R, King M, Izzo E, Koob G F, Pasternak G W
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
Eur J Pharmacol. 1999 Oct 27;383(2):115-9. doi: 10.1016/s0014-2999(99)00633-0.
In mice, 3-O-methylnaltrexone blocks the analgesic actions of morphine-6beta-glucuronide and heroin at doses which are inactive against morphine. We found a similar selectivity in rats. 3-O-Methylnaltrexone antagonized the analgesic actions of 6-acetylmorphine in Sprague-Dawley rats and heroin in Wistar rats at doses that were inactive against morphine. Inclusion of a fixed dose of 3-O-methylnaltrexone significantly shifted the analgesic dose-response curves for 6-acetylmorphine and heroin without altering the morphine dose-response curves. In a self-administration model, 3-O-methylnaltrexone treatment significantly increased both heroin and morphine intake during the first hour, suggestive of an antagonist effect. This effect at doses of 3-O-methylnaltrexone which were inactive against morphine analgesia implied a role for the morphine-6beta-glucuronide opioid receptor in the reinforcing properties of heroin and morphine.
在小鼠中，3 - O - 甲基纳曲酮能阻断吗啡 - 6β - 葡萄糖醛酸苷和海洛因的镇痛作用，而这些剂量对吗啡却无作用。我们在大鼠中也发现了类似的选择性。3 - O - 甲基纳曲酮能拮抗6 - 乙酰吗啡对斯普拉格 - 道利大鼠的镇痛作用以及海洛因对Wistar大鼠的镇痛作用，而这些剂量对吗啡无作用。加入固定剂量的3 - O - 甲基纳曲酮能显著改变6 - 乙酰吗啡和海洛因的镇痛剂量 - 反应曲线，而不改变吗啡的剂量 - 反应曲线。在一个自我给药模型中，3 - O - 甲基纳曲酮治疗在最初一小时内显著增加了海洛因和吗啡的摄入量，提示有拮抗作用。3 - O - 甲基纳曲酮的这些剂量对吗啡镇痛无作用，这表明吗啡 - 6β - 葡萄糖醛酸苷阿片受体在海洛因和吗啡的强化特性中起作用。
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