Plesan A, Hedman U, Xu X J, Wiesenfeld-Hallin Z
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Anesth Analg. 1998 Apr;86(4):825-9. doi: 10.1097/00000539-199804000-00027.
We compared the efficacy of two clinically available drugs with N-methyl-D-aspartate receptor antagonist properties, dextromethorphan and ketamine, in potentiating morphine-induced antinociception. Ketamine alone at 0.3-3 mg/kg had no effect on the hot plate test and at 10 mg/kg caused sedation/motor deficits. The antinociceptive effect of 5 mg/kg morphine was slightly enhanced by 1 mg/kg, but not 0.3 or 3 mg/kg, ketamine. Dextromethorphan alone at 45 mg/kg had no effect, but at 60 mg/kg caused sedation/motor deficit. At 15-45 mg/kg, dextromethorphan significantly and dose-dependently increased the magnitude and duration of morphine-induced antinociception. Dextromethorphan also potentiated morphine at doses that, by themselves, did not cause antinociception (1-2 mg/kg).
Dextromethorphan was more effective than ketamine in potentiating morphine-induced antinociception. Dextromethorphan may thus be the drug of choice for testing the interactions between N-methyl-D-aspartate antagonists and morphine clinically.
我们比较了两种临床上可用的具有N-甲基-D-天冬氨酸受体拮抗剂特性的药物——右美沙芬和氯胺酮，在增强吗啡诱导的镇痛作用方面的效果。单独使用氯胺酮，剂量为0.3 - 3mg/kg时对热板试验无影响，剂量为10mg/kg时会引起镇静/运动功能缺陷。5mg/kg吗啡的镇痛作用在联合使用1mg/kg氯胺酮时略有增强，但联合使用0.3mg/kg或3mg/kg氯胺酮时则无增强效果。单独使用右美沙芬，剂量为45mg/kg时无影响，剂量为60mg/kg时会引起镇静/运动功能缺陷。在15 - 45mg/kg剂量范围内，右美沙芬显著且呈剂量依赖性地增强了吗啡诱导的镇痛作用的强度和持续时间。右美沙芬在自身不引起镇痛作用的剂量（1 - 2mg/kg）下也能增强吗啡的作用。
在增强吗啡诱导的镇痛作用方面，右美沙芬比氯胺酮更有效。因此，右美沙芬可能是临床上测试N-甲基-D-天冬氨酸拮抗剂与吗啡之间相互作用的首选药物。
