NCS-382对丙泊酚、氯胺酮和依托咪酯催眠镇痛作用的影响

目的探讨γ-羟基丁酸受体拮抗剂NCS-382对丙泊酚、氯胺酮和依托咪酯催眠及镇痛作用的影响。方法①催醒实验:120只小鼠分别ip给予丙泊酚200 mg.kg-1、氯胺酮150 mg.kg-1和依托咪酯40mg.kg-1制备催眠模型后,再按分组分别icv给予人工脑脊液(aCSF),NCS-382 1,5和25μg.kg-1,记录睡眠时间。②热板实验:80只小鼠分别ip给予生理盐水10 ml.kg-1和氯胺酮40 mg.kg-1后,再按分组分别ith给予aCSF和NCS-382 1,5和25μg.kg-1,记录热板法痛阈。③扭体实验:80只小鼠分别ip给予生理盐水10 ml.kg-1和氯胺酮40 mg.kg-1后,再按分组分别ith给予aCSF和NCS-382 1,5和25μg.kg-1,1 min后ip给予1.0%冰醋酸溶液10 ml.kg-1,记录15 min内小鼠扭体次数。结果①催醒实验:NS-382 1,5和25μg.kg-1组小鼠的睡眠时间明显缩短,从丙泊酚组的(81±30)min缩短到44±23,40±21,(40±17)min;从氯胺酮组的(19±4)min缩短到8±4,12±3,(15±4)min;从依托咪酯组的(31±11)min缩短到21±9,22±6,(23±10)min;②热板实验:小鼠在给予氯胺酮麻醉后10～30 min痛阈明显长于基础痛阈(P<0.05),NCS-382对氯胺酮所致痛阈延长无改善作用。单用NCS-382对正常小鼠的痛阈无影响;③扭体实验:单用NCS-382对正常小鼠的扭体次数无明显差异;氯胺酮组小鼠扭体次数明显少于正常对照组(P<0.05),给予NCS-382对此无改善作用。结论γ-羟基丁酸受体可能介导了静脉麻醉药丙泊酚、氯胺酮和依托咪酯的催眠作用,但可能与氯胺酮镇痛作用关系不大。

Effects of NCS-382 on hypnosis and analgesia of propofol, ketamine and etomidate in mice

OBJECTIVE To investigate the effect of NCS-382 on hypnosis and analgesia of propofol, ketamine and etomidate in mice. METHODS ① Analeptic test: a total of 120 mice were ip given propofol 200 mg·kg^-1, ketamine 150 mg·kg^-1 and etomidate 40 mg·kg^-1 to establish a hypnosis model, respectively. Then, the mice were icv given aCSF and NCS-382 1, 5 and 25 μg·kg^-1, respectively, and sleeping time was recorded. ② Hot- plate test: a total of 80 mice were ip given normal saline 10 ml·kg^-1 and ketamine 40 mg·kg^-1, respectively, and were ith given aCSF and NCS-382 1, 5 and 25 μg·kg^-1, respectively. The pain threshold in hot-plate test (HPPT) was recorded. ③ Writhing test: a total of 80 mice were respectively ip given normal saline 10 ml·kg^-1 and ketamine 40 mg·kg^-1. Then, the mice were ith given aCSF and NCS-382 1, 5 and 25 μg·kg^-1, respectively. They were ip given 1.0% acetic acid 10 ml·kg^-1, then writhing time within 15 min were recorded. RESULTS Analeptic test: the sleeping time in NCS-382 1.5 and 25 μg·kg^-1 groups was significantly shortened by propofol for (81±30)min to 44±23, 40±21 and (40±17)min, by ketamine for (19±4)min to 8±4, 12±3 and (15±4)min; by etomidate for (31±11)min to 21±9, 22±6 and (23±10)min. ② Hot-plate test: compared with self basal HPPT, ketamine could significantly prolong HPPT 10-30 min after administration (P<0.05). NCS- 382 had no effect on the prolonged HPPT by ketamine. ③ Writhing test: compared with normal control group, NCS- 382 had no effect on writhing times. The writhing times in ketamine groups decreased significantly. NCS-382 had no effect on the increased writhing times induced by ketamine. CONCLUSION NCS-382 may mediate the hypnotic effect of propofol, ketamine and etomidate, but it may have little analgesic effect as ketamine does.