(R)-Ketamine Induces a Greater Increase in Prefrontal 5-HT Release Than (S)-Ketamine and Ketamine Metabolites via an AMPA Receptor-Independent Mechanism
The International Journal of Neuropsychopharmacology July 16, 2019 Yukio Ago, Wataru Tanabe, Momoko Higuchi et al. 91 citations
Ketamine enantiomers and their metabolites differentially affect monoamine neurotransmitter release in the mouse prefrontal cortex. (R)-ketamine more strongly increases serotonin release than (S)-ketamine, while (S)-ketamine produces a larger increase in dopamine release. Both enantiomers increase noradrenaline release to a similar extent. The metabolite (2R,6R)-HNK slightly increases serotonin and noradrenaline but not dopamine release, whereas (S)-NK increases dopamine and noradrenaline but not serotonin. An AMPA receptor antagonist blocks (S)-ketamine-induced serotonin release and dopamine release by both enantiomers, but not (R)-ketamine-induced serotonin release, indicating (R)-ketamine acts through an AMPA receptor-independent mechanism. These findings reveal neurochemical differences underlying the pharmacological profiles of ketamine enantiomers and their metabolites.