Wong C L, Roberts M B, Wai M K
Eur J Pharmacol. 1980 Jun 27;64(4):289-95. doi: 10.1016/0014-2999(80)90236-8.
Morphine caused a dose-dependent slowing of the rate of intestinal transit in mice. This inhibitory effect of morphine was antagonised by naloxone administration. Pretreatment with a single dose of morphine did not induce any detectable tolerance to the inhibitory effect of a second dose of morphine given 5 h later. However, naloxone was more effective in antagonising this inhibitory effect of morphine in morphine-pretreated mice than in saline-pretreated animals. Molecular sieve morphine pellet implantation for 24 h induced detectable tolerance to the inhibitory effect of morphine administered 3 h after removal of the pellet. In addition, the antagonistic effect of naloxone was also augmented when compared with blank pellet-implanted control animals. The present study has shown that the enhanced naloxone potency against the inhibitory effect of morphine was intestinal transit was observalbe before the development of overt tolerance, and that tolerance to the effect of morphine on the small intestine could be induced by implantation of a molecular sieve morphine pellet for 24 h.
吗啡可使小鼠肠道传输速率呈剂量依赖性减慢。纳洛酮给药可拮抗吗啡的这种抑制作用。单次给予吗啡预处理不会诱导对5小时后给予的第二剂吗啡的抑制作用产生任何可检测到的耐受性。然而，与生理盐水预处理的动物相比，纳洛酮在拮抗吗啡预处理小鼠中吗啡的这种抑制作用方面更有效。植入分子筛吗啡微丸24小时可诱导对去除微丸3小时后给予的吗啡的抑制作用产生可检测到的耐受性。此外，与植入空白微丸的对照动物相比，纳洛酮的拮抗作用也增强了。本研究表明，在明显耐受性出现之前，肠道传输就可观察到纳洛酮针对吗啡抑制作用的效力增强，并且植入分子筛吗啡微丸24小时可诱导对吗啡对小肠作用的耐受性。
