氟胺酮和氯胺酮的毒性比较研究

Comparative Study of the Toxicity of 2-fluorodeschloroketamine and Ketamine

目的:分析氟胺酮和氯胺酮的急性毒性及神经毒性作用。方法:急性毒性实验采用“上下法”给药,观察小鼠给予氟胺酮或氯胺酮2 d内的反应,并计算半数致死量(median lethal dose,LD_(50))。神经毒性实验则采用MTT法观察氟胺酮或氯胺酮对神经细胞的毒性作用,并计算半数抑制浓度(half maximal inhibitory concentration,IC_(50))。结果:氟胺酮的小鼠4种给药方式LD_(50)值大小顺序与氯胺酮的一致,依次为尾静脉给药<腹腔给药<皮下给药<灌胃给药。氟胺酮和氯胺酮的LD_(50)均值分别为294.00 mg/kg和241.78 mg/kg。氟胺酮对SH-SY5Y、PC12和SN4741三种细胞系的IC_(50)值依次为7.91 mmol/L、17.63 mmol/L和18.18 mmol/L,与氯胺酮的IC_(50)值大小顺序一致。氟胺酮和氯胺酮的IC_(50)均值分别为14.57 mmol/L和4.55 mmol/L。结论:以LD_(50)和IC_(50)均值为标准,氟胺酮的急性毒性为氯胺酮的82.24%,而其神经毒性为氯胺酮的31.23%,上述结果表明氟胺酮的毒性小于氯胺酮,但其危害性不容忽视。

Objective:To study of the acute toxicity and neurotoxic effects of 2-fluorodeschloroketamine(2-FDCK)and ketamine.Methods:In the acute toxicity experiment,the“up and down dose method”was used to observe the mice’s response to 2-FDCK or ketamine within 2 days,and the median lethal dose(LD_(50))was calculated.In the neurotoxicity experiment,the MTT method was used to observe the toxic effects of 2-FDCK or ketamine on neuronal cells,and the half maximal inhibitory concentration(IC_(50))was calculated.Results:The LD_(50)value order of the four administration modes of 2-FDCK in mice was the same as that of ketamine,tail vein administration<intraperitoneal administration<subcutaneous administration<intragastric administration.The average LD_(50)values of 2-FDCK and ketamine were 294 mg/kg and 241.78 mg/kg,respectively.The IC_(50)values of 2-FDCK for SH-SY5Y cells,PC12 cells,SN4741 cells were 7.91 mmol/L,17.63 mmol/L and 18.18 mmol/L,respectively.The IC_(50)values order of 2-FDCK was the same as that of ketamine.The average IC_(50)values of 2-FDCK and ketamine were 14.57 mmol/L and 4.55 mmol/L,respectively.Conclusion:Based on the average value of LD_(50)and IC_(50),the acute toxicity of 2-FDCK is 82.24%that of ketamine,and its neurotoxicity is 31.23%that of ketamine,which indicated that the toxicity of 2-FDCK is less than that of ketamine,but its harmfulness cannot be ignored.