Jayaram A, Singh P, Noreuil T, Fournié-Zaluski M C, Carp H M
Department of Anesthesiology, Oregon Health Sciences University, Portland 97210-3098, USA.
Anesth Analg. 1997 Feb;84(2):355-8. doi: 10.1097/00000539-199702000-00021.
In an earlier study, we demonstrated the enhancement of pregnancy-induced analgesia with an inhibitor of endogenous enkephalin metabolism. The purpose of the present study was to evaluate the antinociceptive effect of another inhibitor of enkephalin metabolism, RB 101, on pregnant mice. Further, since other studies have shown RB 101 to be free of opioid side effects, we examined its effect on respiratory rate. Analgesia was assessed using the hot plate test, and respiratory rate was measured by recording the output from an end-tidal carbon dioxide detector. In pregnant mice, experiments were conducted on Day 17 or Day 18 of pregnancy; mice usually deliver on Day 19. For the hot plate test, animals were tested in the following groups: Group 1, RB 101 150 mg/kg (n = 15); Group 2, RB 101 50 mg/kg (n = 15); Group 3, RB 101 vehicle (n = 15); Group 4, morphine 5 mg/kg (n = 14); and Group 5, RB 101 150 mg/kg + naloxone 5 mg/kg (n = 10). The test was repeated on the second day after delivery in animals in Groups 1 and 3 (given RB 101 150 mg/kg and RB 101 vehicle, respectively). RB 101 150 mg/kg and morphine 5 mg/kg were significantly different (mean percentage of maximum possible effect 30.0 and 37.7, respectively, at 30 min and 41.6 and 32.6, respectively, at 60 min) in their antinociceptive effect in pregnant animals from all other groups. Naloxone, when coadministered with RB 101, prevented the development of antinociception. RB 101 150 mg/kg was not antinociceptive after delivery. Depression of respiratory rate was tested in a separate set of animals in the following groups: Group 1, RB 101 150 mg/kg (n = 16); Group 2, morphine 5 mg/kg (n = 16); Group 3, RB 101 vehicle (n = 15). Morphine 5 mg/kg produced significant depression of respiratory rate at 30 min postinjection when compared with RB 101 150 mg/kg and RB 101 vehicle (mean percent change in respiratory rate was 78.5% compared with 87.7% and 92.4%, respectively, where 100% = no change). These results suggest that drugs such as RB 101 may produce antinociception with minimal effects on respiration.
在一项早期研究中，我们证明了使用内源性脑啡肽代谢抑制剂可增强妊娠诱导的镇痛作用。本研究的目的是评估另一种脑啡肽代谢抑制剂RB 101对妊娠小鼠的镇痛作用。此外，由于其他研究表明RB 101没有阿片类药物的副作用，我们检测了它对呼吸频率的影响。使用热板试验评估镇痛效果，通过记录呼气末二氧化碳检测仪的输出测量呼吸频率。对于妊娠小鼠，在妊娠第17天或第18天进行实验；小鼠通常在第19天分娩。对于热板试验，将动物分为以下几组进行测试：第1组，RB 101 150 mg/kg（n = 15）；第2组，RB 101 50 mg/kg（n = 15）；第3组，RB 101赋形剂（n = 15）；第4组，吗啡5 mg/kg（n = 14）；第5组，RB 101 150 mg/kg + 纳洛酮5 mg/kg（n = 10）。在第1组和第3组动物（分别给予RB 101 150 mg/kg和RB 101赋形剂）分娩后的第二天重复该试验。在妊娠动物中，RB 101 150 mg/kg和吗啡5 mg/kg的镇痛效果与所有其他组有显著差异（在30分钟时，最大可能效应的平均百分比分别为30.0和37.7，在60分钟时分别为41.6和32.6）。当与RB 101共同给药时，纳洛酮可防止镇痛作用的产生。分娩后，RB 101 150 mg/kg没有镇痛作用。在另一组单独的动物中测试呼吸频率的降低，分组如下：第1组，RB 101 150 mg/kg（n = 16）；第2组，吗啡5 mg/kg（n = 16）；第3组，RB 101赋形剂（n = 15）。与RB 101 150 mg/kg和RB 101赋形剂相比，注射后30分钟时，吗啡5 mg/kg可使呼吸频率显著降低（呼吸频率的平均变化百分比为78.5%，而RB 101 150 mg/kg和RB 101赋形剂分别为87.7%和92.4%，其中100% = 无变化）。这些结果表明，像RB 101这样的药物可能产生镇痛作用，同时对呼吸的影响最小。
