Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine.
Pharmacology, Biochemistry and Behavior June 1, 2019 Lijia Chang, Kai Zhang, Yaoyu Pu et al. 174 citations
In a mouse model of chronic social defeat stress, a single intranasal dose of (R)-ketamine produced stronger antidepressant effects than (R,S)-ketamine or (S)-ketamine. Conversely, (S)-ketamine caused the greatest increase in locomotor activity and deficits in prepulse inhibition, followed by (R,S)-ketamine, while (R)-ketamine showed the least. In conditioned place preference tests, repeated intranasal (S)-ketamine and (R,S)-ketamine increased preference scores dose-dependently, indicating abuse liability, whereas (R)-ketamine did not. These findings suggest intranasal (R)-ketamine may be a safer antidepressant option.