Neil A
Naunyn Schmiedebergs Arch Pharmacol. 1982 Jul;320(1):50-3. doi: 10.1007/BF00499071.
Mice were rendered tolerant to morphine or 1-methadone by subcutaneous injections for 4 days. The antinociceptive activities of morphine, codeine, l-methadone and d-propoxyphene were determined in tolerant and control mice using the hot-plate test, and the respective ED50's were calculated by the up-and-down procedure of Dixon. An asymmetry in cross-tolerance patterns was found: While morphine-pretreated mice were tolerant to morphine only (with a dose-ratio tolerant: control of 5.2), methadone-pretreated mice were tolerant to all analgesics tested, and more so to morphine 5.2; l-methadone 3.0; codeine 2.7 and d-propoxyphene 1.9). The results are discussed in terms of heterogeneity in opioid receptor mechanisms.
通过皮下注射4天使小鼠对吗啡或1-美沙酮产生耐受性。使用热板试验测定了耐受性小鼠和对照小鼠中吗啡、可待因、l-美沙酮和d-丙氧芬的抗伤害感受活性，并通过Dixon的上下法计算各自的半数有效剂量（ED50）。发现交叉耐受性模式存在不对称性：虽然用吗啡预处理的小鼠仅对吗啡产生耐受性（耐受性与对照的剂量比为5.2），但用美沙酮预处理的小鼠对所有测试的镇痛药均产生耐受性，对吗啡的耐受性更高（5.2）；l-美沙酮为3.0；可待因为2.7；d-丙氧芬为1.9）。根据阿片受体机制的异质性对结果进行了讨论。
