Pharmacological Properties of the Optical Isomers of Ketamine
The hypnotic effects of intravenous racemic ketamine and of its (+) and (-) isomers were examined in the ICR mouse at dosages of 10 mg/kg to 40 mg/kg. At equimolar doses (25 mg/kg) the duration of hypnosis was 4.0, 5.3 and 1.9 minutes for racemic ketamine and the (+) and (-) isomers respectively. Following 25 mg/kg of racemic ketamine, brain and plasma levels of the drug were 22 μg/g and 4.6 μg/ml respectively at recovery of righting reflex. Dose/response curves were obtained for analgesic activity in the mouse using the phenylquinone writhing test. The AD50 for racemic ketamine following subcutaneous administration was 6.5 mg/kg. At equimolar doses the (+) isomer was approximately 2 × as potent in terms of analgesia as the race-mate while the (-) isomer lacked significant analgesic activity. Previously this laboratory has reported significant differences in hypnotic and locomotor activity between (+) and (-) ketamine in the Sprague-Dawley rat. The present study shows that such differences can occur in other animal species and in addition demonstrates significant differences in the analgesic activity of the two isomers. (Supported in part by NIDA grant no. DA00006).