Comparison of psychic emergence reactions after (±)-ketamine and (+)-ketamine in mice

Ketamine is a racemic mixture containing equal parts of (+)-ketamine and (-)-ketamine. The ketamine enantiomorphs are different in anesthesia and psychic emergence reactions after anesthesia. Therefore, (+)-ketamine was compared with racemic ketamine in a number of randomized studies in volunteers and patients. However, their relations remain controversial. In the present studies, the psychic emergence reactions after injection of (+/-)-ketamine and (+)-ketamine were compared in mice. At equimolar doses, the (+)-isomers elicited episodes of hypnosis nearly 1.4-fold more potent than those of the racemic ketamine. After the administration of equihypnotic doses of (+)ketamine and ketamine, the posthypnotic stimulation of locomotor activity, stereotype behavior and 5-HT-induced head-twitch response by the enantiomorph was significantly less intense than that of racemic ketamine. In receptor binding test, (+)-ketamine showed a higher affinity for NMDA receptor than that of ()-ketamine, while (+)-ketamine and (+/-)-ketamine showed no affinity for dopamine D-2 and serotonin 5-HT, receptor. These results suggest that the (+)-ketamine has fewer posthypnotic side effects than (+/-)-ketamine when (+)-ketamine and (+)-ketamine were administered at equihypnotic dosages and that dopamine D, and serotonin 5-HT, receptor were not involved in the effects of (+)-ketamine and (+/-)-ketamine. (c) 2005 Elsevier Inc. All rights reserved.