Bhargava H N
Anesthesiology. 1979 Nov;51(5):398-401. doi: 10.1097/00000542-197911000-00006.
In an attempt to ascertain whether opiate receptors and brain enkephalins or endorphins are involved in pentobarbital anesthesia and toxicity, the effects of 1) two pure narcotic antagonists, naloxone and naltrexone, 2) morphine sulfate, 3) D-phenylalanine, an inhibitor of carboxypeptidase A, and 4) D-leucine, an inhibitor of leucineaminopeptidase, in combination with D-phenylalanine, were studied in mice. Both naloxone and naltrexone, (1, 5 and 10 mg/kg) administered subcutaneously to mice were unable to modify the duration of anesthesia when they were injected 5 min prior to a challenge dose (75 mg/kg) of pentobarbital (ip). The onset of anesthesia was unaltered by naloxone (1, 5 and 10 mg/kg) and naltrexone (1 mg/kg). Higher doses of naltrexone (5 and 10 mg/kg) delayed the onset of anesthesia slightly. Morphine (1, 2.5 and 5 mg/kg) given 30 min before pentobarbital did not modify the onset or the duration of anesthesia. D-Phenylalanine (250 mg/kg), and D-phenylalanine + D-leucine (250 mg/kg each) injected ip an hour before pentobarbital did not affect either onset or duration of anesthesia. Naltrexone (10 mg/kg, ip) given 5 min before pentobarbital did not alter the LD50 of the latter. The studies do not support a role of enkephalins or endorphins in pentobarbital anesthesia or toxicity, and suggest a need for caution in using narcotic antagonists in treating pentobarbital toxicity.
为了确定阿片受体以及脑内啡肽或内啡肽是否参与戊巴比妥麻醉和毒性作用，研究了以下几种药物对小鼠的影响：1）两种纯麻醉拮抗剂，纳洛酮和纳曲酮；2）硫酸吗啡；3）D-苯丙氨酸，一种羧肽酶A抑制剂；4）D-亮氨酸，一种亮氨酸氨肽酶抑制剂，与D-苯丙氨酸联合使用。给小鼠皮下注射纳洛酮和纳曲酮（1、5和10mg/kg），在给予戊巴比妥（腹腔注射，75mg/kg）激发剂量前5分钟注射，均不能改变麻醉持续时间。纳洛酮（1、5和10mg/kg）和纳曲酮（1mg/kg）不改变麻醉诱导期。更高剂量的纳曲酮（5和10mg/kg）略微延迟麻醉诱导期。在戊巴比妥给药前30分钟给予吗啡（1、2.5和5mg/kg），不改变麻醉诱导期或持续时间。在戊巴比妥给药前1小时腹腔注射D-苯丙氨酸（250mg/kg）以及D-苯丙氨酸+D-亮氨酸（各250mg/kg），对麻醉诱导期或持续时间均无影响。在戊巴比妥给药前5分钟腹腔注射纳曲酮（10mg/kg），不改变戊巴比妥的半数致死量。这些研究不支持脑内啡肽或内啡肽在戊巴比妥麻醉或毒性中起作用，并提示在使用麻醉拮抗剂治疗戊巴比妥中毒时需谨慎。
