Yaksh T L, Noueihed R Y, Durant P A
Anesthesiology. 1986 Jan;64(1):54-66. doi: 10.1097/00000542-198601000-00009.
In rats, intrathecal alfentanil, lofentanil, sufentanil, fentanyl, and morphine produced dose-dependent elevations in the hot-plate and tail-flick latencies and a powerful suppression of the writhing response. The slopes of the monotonic dose-response curves for the five opioids did not differ significantly. In terms of the hot-plate ED50 after intrathecal injection, the order of potency was as follows: lofentanil (210), sufentanil (29), fentanyl (3), morphine (1), and alfentanil (1). Comparable results were observed in the tail flick. The duration of action was proportional to dose. However, at doses that produced an equal magnitude of inhibition, the duration of action was lofentanil greater than morphine greater than sufentanil greater than alfentanil greater than or equal to fentanyl. Systemically administered naloxone (0.03-1 mg/kg, sc) resulted in dose-dependent antagonism of the antinociceptive effect of intrathecal morphine, fentanyl, alfentanil, and sufentanil. In contrast, intrathecal lofentanil was extremely resistant to antagonism by naloxone. In cats, similar dose-dependent blockade of the thermally evoked skin-twitch response was observed after intrathecal morphine, sufentanil, alfentanil, and fentanyl. As in the rat, the slope of the monotonic dose-response curves did not differ. The relative potency and duration of action after equipotent intrathecal doses were similar to those observed in the rodent. These results suggest that sufentanil, alfentanil, and fentanyl exert their analgesic effects in vivo at a spinal cord site that has properties comparable to those of the site acted upon by morphine. Except for catalepsy in rats, no major behavioral dysfunctions were noted at the ED50 dose of any of the drugs administered. No abnormal morphologic effects of acutely or chronically administered alfentanil and sufentanil were seen, aside from an inflammatory reaction secondary to catheter placement.
在大鼠中，鞘内注射阿芬太尼、洛芬太尼、舒芬太尼、芬太尼和吗啡可使热板法和甩尾法的潜伏期呈剂量依赖性延长，并强烈抑制扭体反应。这五种阿片类药物的单调剂量-反应曲线斜率无显著差异。就鞘内注射后的热板法半数有效剂量（ED50）而言，效价顺序如下：洛芬太尼（210）、舒芬太尼（29）、芬太尼（3）、吗啡（1）和阿芬太尼（1）。甩尾法观察到类似结果。作用持续时间与剂量成正比。然而，在产生同等程度抑制的剂量下，作用持续时间为洛芬太尼＞吗啡＞舒芬太尼＞阿芬太尼≥芬太尼。全身注射纳洛酮（0.03 - 1mg/kg，皮下注射）可导致鞘内吗啡、芬太尼、阿芬太尼和舒芬太尼的镇痛作用出现剂量依赖性拮抗。相比之下，鞘内注射洛芬太尼对纳洛酮的拮抗作用具有极强的耐受性。在猫中，鞘内注射吗啡、舒芬太尼、阿芬太尼和芬太尼后，观察到类似的剂量依赖性热诱发皮肤抽搐反应阻断。与大鼠一样，单调剂量-反应曲线斜率无差异。鞘内等剂量给药后的相对效价和作用持续时间与在啮齿动物中观察到的相似。这些结果表明，舒芬太尼、阿芬太尼和芬太尼在体内通过作用于脊髓部位发挥镇痛作用，该部位的特性与吗啡作用的部位相当。除了大鼠出现僵住症外，在所给予的任何药物的ED50剂量下均未观察到主要的行为功能障碍。除了导管置入继发的炎症反应外，未观察到急性或慢性给予阿芬太尼和舒芬太尼的异常形态学效应。
