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Updated: May 9, 2026

Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Structure-activity relationships for ketamine esters as short-acting anaesthetics
Jiney Jose1, Swarna A Gamage, Martyn G Harvey
1Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
Abstract:
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.
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