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Yukihiko Shirayama

2 papers in the library · 713 citations · publishing 2015-2017

Papers

R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects

Translational Psychiatry September 1, 2015 Chun Yang, Yukihiko Shirayama, J-C Zhang et al. 600 citations

R-ketamine, a stereoisomer of the anesthetic ketamine, produces a more potent and longer-lasting antidepressant effect than S-ketamine (esketamine) in mouse models of depression, without causing psychotomimetic side effects or abuse liability. In the social defeat stress and learned helplessness models, R-ketamine more effectively restored decreased dendritic spine density, brain-derived neurotrophic factor (BDNF)-TrkB signaling, and synaptogenesis in the prefrontal cortex, CA3, and dentate gyrus of the hippocampus. Neither isomer affected these measures in the nucleus accumbens. S-ketamine, but not R-ketamine, caused hyperlocomotion, prepulse inhibition deficits, rewarding effects, and loss of parvalbumin-positive cells in the medial prefrontal cortex and dentate gyrus. R-ketamine appears to be a safe, long-lasting antidepressant.

DOI: 10.1038/tp.2015.136 Full text Ketamine Psychotomimetic Antidepressant Nucleus accumbens +11

Lack of Antidepressant Effects of (2R,6R)-Hydroxynorketamine in a Rat Learned Helplessness Model: Comparison with (R)-Ketamine

The International Journal of Neuropsychopharmacology November 14, 2017 Yukihiko Shirayama, Kenji Hashimoto 113 citations

A single dose of (R)-ketamine (20 mg/kg) produced an antidepressant effect in a rat learned helplessness model of depression. In contrast, neither (R)-norketamine (20 mg/kg) nor (2R,6R)-hydroxynorketamine (20 and 40 mg/kg) showed such effects. These results indicate that the metabolism of ketamine to hydroxynorketamine is not essential for its antidepressant actions, contradicting previous claims.

DOI: 10.1093/ijnp/pyx108 Full text Ketamine Learned helplessness Antidepressant Pharmacology +6