Antagonistic effect of physostigmine on ketamine-induced anesthesia

Effects of physostigmine on ketamine-induced anesthesia and analgesia were studied in male Sprague-Dawley rats using behavioral tests. Rats were divided into six groups. Immediately after loss of the righting reflex following an intraperitoneal injection of ketamine 75 mg/kg, each group of rats was given an intraperitoneal injection of either physostigmine 0.05, 0.1, 0.2, 0.4, 0.6 mg/kg or saline as the control, respectively. Physostigmine 0.1 mg/kg caused the greatest antagonistic effect on ketamine anesthesia as indicated by sleeping time, duration of ataxia and motor coordination. The antagonistic effects of physostigmine were reduced by a dose of physostigmine of greater than 0.1 mg/kg. However, at no dose did physostigmine antagonize ketamine analgesia as indicated by the tail-flick latency. Physostigmine (0.4 and 0.6 mg/kg) itself had analgesic and motor-suppressive actions. It can therefore be presumed that there is a limited threshold of the dose of physostigmine which develops an antagonistic effect on ketamine anesthesia due to the motor-suppressive action. It is also confirmed that physostigmine itself produces analgesia, and does not antagonize ketamine-induced analgesia.