Ketamine is a mixture of equal amounts of two enantiomers: esketamine and arketamine. Esketamine is a more potent NMDA receptor antagonist and dissociative hallucinogen than arketamine. Because of the hypothesis that NMDA receptor antagonism underlies the antidepressant effects of ketamine, esketamine was developed as an antidepressant. However, multiple other NMDA receptor antagonists, including memantine, lanicemine, rislenemdaz, rapastinel, and 4-chlorokynurenine, have thus far failed to demonstrate sufficient effectiveness for depression. Furthermore, animal research indicates that arketamine, the enantiomer with a weaker NMDA receptor antagonism, as well as (2"R",6"R")-hydroxynorketamine, the metabolite with negligible affinity for the NMDA receptor but a potent alpha-7 nicotinic receptor antagonist may have antidepressive action. It is now argued that NMDA receptor antagonism may not be responsible for the antidepressant effects of ketamine.