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It has been commonly believed that the antidepressant effects of ketamine are due to its antagonism at the N-methyl-D-aspartate (NMDA) receptor, but the current researchers explored other possibilities in mouse models. Several authors have patent interests in ketamine metabolites.
The researchers examined the differing properties of ketamine's R- and S-enantiomers (right-spiraling and left-spiraling structures with “chiral” [i.e., nonsuperimposable] mirror images). Although the S-enantiomer is more potent at NMDA inhibition, the R-enantiomer had greater antidepressant action. Furthermore, another NMDA antagonist, the experimental drug MK801, did not exhibit antidepressant actions. Thus, NMDA inhibition did not seem to be the mechanism for ke…