Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Bioorg Med Chem. 2013 Sep 1;21(17):5098-106. doi: 10.1016/j.bmc.2013.06.047. Epub 2013 Jun 27.
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.
一系列非阿片类麻醉/镇痛氯胺酮的脂族酯类被制备，并在输注大鼠模型中探索它们作为氯胺酮本身的更短作用类似物的特性，测量从麻醉（翻正反射）和镇痛（对刺激的反应）作用中恢复的时间。酯类作为镇静剂的效力与链长没有显著关系，但 Me、Et 和 i-Pr 酯类的效价更高（比氯胺酮低两倍），而 n-Pr 酯类的效价较低（比氯胺酮低 2-6 倍）。对于 Me、Et 和 i-Pr 酯类，从麻醉中恢复的速度比从氯胺酮本身快 10-15 倍，而对于 n-Pr 酯类，从氯胺酮恢复的速度快 20-25 倍。一种新的二甲氨基氯胺酮衍生物（同型氯胺酮）具有氯胺酮样的镇静作用，但效力稍弱，但同型氯胺酮的酯类类似物具有非常弱的镇静作用。
