White P F, Schüttler J, Shafer A, Stanski D R, Horai Y, Trevor A J
Br J Anaesth. 1985 Feb;57(2):197-203. doi: 10.1093/bja/57.2.197.
The clinical and electroencephalographic (EEG) effects of the individual ketamine isomers were compared with the racemic mixture in five volunteers who received each drug on a separate occasion. Racemic ketamine 275 +/- 25 mg, s(+) ketamine 140 +/- 21 mg or R(-) ketamine 429 +/- 37 mg produced an anaesthetic state lasting 6 +/- 2 min (mean +/- SD). However, the EEG evaluation of the R(-) isomer revealed less overall slowing, and an absence of the large slow wave complexes produced by the S(+) isomer and the racemic mixture. The pharmacokinetic profiles for the individual isomers of ketamine did not differ significantly from the racemic mixture. Even though the apparent anaesthetic state produced in these healthy volunteers did not differ qualitatively between the three drug groups, recovery times (assessed using a standardized battery of psychometric tests) were consistently shorter following the individual isomers compared with the racemic mixture. The serum ketamine concentrations associated with regaining consciousness and orientation were consistent with an S(+):R(-) isomer potency ratio of 4:1. In terms of their ability to impair psychomotor function, the S(+):R(-) potency ratio varied from 3:1 to 5:1. After comparable degrees of CNS depression, we conclude that the more potent S(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.
在五名志愿者身上，将氯胺酮各异构体与消旋混合物的临床及脑电图（EEG）效应进行了比较，每位志愿者在不同时间分别接受每种药物。消旋氯胺酮275±25毫克、S（+）氯胺酮140±21毫克或R（-）氯胺酮429±37毫克均可产生持续6±2分钟（均值±标准差）的麻醉状态。然而，对R（-）异构体的EEG评估显示，整体减慢程度较小，且不存在S（+）异构体和消旋混合物所产生的大慢波复合波。氯胺酮各异构体的药代动力学特征与消旋混合物相比无显著差异。尽管在这些健康志愿者身上产生的明显麻醉状态在三个药物组之间在性质上并无不同，但与消旋混合物相比，各异构体后的恢复时间（使用标准化的心理测量测试组合进行评估）始终较短。与恢复意识和定向相关的血清氯胺酮浓度与S（+）:R（-）异构体效价比为4:1一致。就其损害精神运动功能的能力而言，S（+）:R（-）效价比在3:1至5:1之间变化。在中枢神经系统产生相当程度的抑制后，我们得出结论，与目前使用的消旋混合物相比，氯胺酮中效力更强的S（+）异构体与精神运动技能的更快恢复相关。
