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 ① 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(P0.05).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.