Structure-activity relationships for ketamine esters as short-acting anaesthetics
详细信息 查看全文
- 作者：Jiney Jose ; Swarna A. Gamage ; Martyn G. Harvey ; Logan J. Voss ; James W. Sleigh ; William A. Denny
- 关键词：DCM ; dichloromethane ; LRR ; loss of righting reflex ; NMDA ; N-methyl-d-aspartate ; PWR ; pedal withdrawal reflex score
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2013
- 出版时间：1 September, 2013
- 年：2013
- 卷：21
- 期：17
- 页码：5098-5106
- 全文大小：684 K
文摘
A series of aliphatic esters of the non-opioid anaesthetic/analgesic ketamine were prepared and their properties as shorter-acting analogues of ketamine itself were explored in an infused rat model, measuring the time after infusion to recover from both the anaesthetic (righting reflex) and analgesic (response to stimulus) effects. The potency of the esters as sedatives was not significantly related to chain length, but Me, Et and i-Pr esters were the more dose potent (up to twofold less than ketamine), whereas n-Pr esters were less potent (from 2- to 6-fold less than ketamine). For the Me, Et and i-Pr esters recovery from anaesthesia was 10-15-fold faster than from ketamine itself, and for the n-Pr esters it was 20-25-fold faster than from ketamine. A new dimethylamino ketamine derivative (homoketamine) had ketamine-like sedative effects but was slightly less potent than, but ester analogues of homoketamine had very weak sedative effects.