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(2R,6R)-HNK HCl (1) was synthesized and characterized as described (Morris et al., 2017; Zanos et al., 2016). Prodrug esters (acetate (2a), propionate (2b), pentanoate (2c), octanoate (2d), and benzoate (2e) esters) of (2R,6R)-HNK, substituted at the hydroxyl group, were synthesized and characterized (see Supplementary Material) at the National Center for Advancing Translational Sciences (National Institutes of Health, Rockville, Maryland, USA). Ketamine HCl was purchased from Sigma-Aldrich (USA). All drugs were dissolved in 0.9% saline.
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