Influences of Scopolamine on analgesic,hypnotic and median lethal dose of Ketamine

Objective To investigate the influences of scopolamine on the analgesic,hypnotic and the median lethal dose (LD50) of ketamine.Methods Totally 40 mice were evenly divided into blank group,S+NS group (scopolamine hydrobromide injection 4.5 mg/kg+0.9% sodium chloride solution 0.04 mg/10 g),K+NS group (ketamine hydrochloride injection 20 mg/kg+0.9% sodium chloride solution 0.15 mL/10 g),and S+K group (ketamine hydrochloride injection 4.5 mg/kg+scopolamine hydrobromide injection 20 mg/kg).Hot-plate test,hot tail-flick method and writhing were used to observe the influences of scopolamine on the hypnotic effects of ketamine.The ketamine dosage increased to 60 mg/kg and the influence of scopolamine on hypnotic effects of ketamine was also observed.Three minutes after tail injection of 4.5 mg/kg scopolamine,ketamine was injected into the abdominal cavity;and sequential method (the Dixon-Mood law) was used to determine the influence of scopolamine on the ketamine LD50 and calculate 95% confidence interval (CI).Results For the results of the hot-plate and tail-flick experiment,S+NS group and the blank group had no significant differences in pain threshold in hot-plate test (HPPT) at 5,10,20,and 30 min (P0.05),but the HPPT were significantly lower than those in the S+K group at 5,10 min (P0.05,0.01).As for the results of the writhing test,the number of writhing in the blank group,S+NS,and K+NS group were (56±11),(60±6),and (33±5) times,respectively and they were significantly higher than that of the S+K group (8±5) times (P0.01).For the hypnosis experiment,there was no significant difference in the latency and sleeping time between the S+NS group and the blank group (P0.05);compared with the blank group and S+NS group,the latency of S+K group was significantly shorter (P values are 0.01) and sleeping time was significantly prolonged (P0.01).The value of LD50 was 259.9 mg/kg and 95% CI was 195.7-345.5 mg/kg in NS+K group.The values of LD50,95% CI of S+K group were 320.1 mg/kg and 214.1-478.0 mg/kg,respectively,but there were no significant difference between the two groups (P0.05).Conclusion Scopolamine can enhance the analgesic,hypnotic effects of ktamine,and does not increase its toxicity.(Shanghai Med J,2010,33:325-328)