NMDAR ligand binding and functional inhibition
Ketamine Ki and IC50 values are only reported from studies that compared the effects of ketamine to HNKs under similar experimental conditions.
Compound | Affinity/Potency | References | |||
---|---|---|---|---|---|
NMDAR binding affinity (MK-801 displacement) | |||||
(R,S)-ketamine | Ki = 0.25–1.06 µM | Moaddel et al. (2013); Morris et al. (2017) | |||
(2S,6S)-HNK | Ki = 7.34–21.19 µM | ||||
(2R,6R)-HNK | Ki > 100 µM | ||||
(2R,5R)-HNK | Ki > 100 µM | ||||
(2S,5S)-HNK | Ki > 100 µM | ||||
(2R,5S)-HNK | Ki > 100 µM | ||||
(2S,5R)-HNK | Ki > 100 µM | ||||
(2R,4R)-HNK | Ki > 100 µM | ||||
(2S,4S)-HNK | Ki > 100 µM | ||||
(2R,4S)-HNK | Ki > 100 µM | ||||
(2S,4R)-HNK | Ki > 100 µM | ||||
(2R,6R)-HNK | Ki > 10 µM | Zanos et al. (2016) | |||
(2S,6S)-HNK | Ki > 10 µM | ||||
Inhibition of NMDAR-mediated current amplitude, X. laevis oocytes | |||||
GluN subunits | 1A/2A | 1A/2B | 1A/2C | 1A/2D | |
(R,S)-ketamine | IC50 = 3.3 µM | IC50 = 0.9 µM | IC50 = 1.7 µM | IC50 = 2.4 µM | Dravid et al. (2007); Lumsden et al. (2019) |
(2R,6R)-HNK | IC50 = 498 µM | IC50 = 258 µM | IC50 = 202 µM | IC50 = 287 µM | |
(2S,6S)-HNK | IC50 = 43 µM | IC50 = 21 µM | IC50 = 15 µM | 13 µM | |
Inhibition of NMDAR-mediated current amplitude, HEK-293 cells | |||||
GluN subunits | 1A/2A | 1A/2B | |||
(R,S)-ketamine | IC50 = 0.8 µM at pH 6.8 | ND | Abbott and Popescu (2020) | ||
IC50 = 0.5 µM at pH 7.2 | |||||
(2R,6R)-HNK | IC50 = 46 µM at pH 6.8 | IC50 = 39 µM at pH 6.8 | |||
IC50 = 46 µM at pH 7.2 | IC50 = 69 µM at pH 7.2 | ||||
Inhibition of NMDAR-mediated fEPSP slope, SC-CA1 mouse hippocampal slices | |||||
(R,S)-ketamine | IC50 = 4.5 µM | Lumsden et al. (2019) | |||
(2R,6R)-HNK | IC50 = 211.9 µM | ||||
(2S,6S)-HNK | IC50 = 47.2 µM | ||||
Inhibition of NMDAR-mediated mEPSC amplitude, CA1 neurons in rat hippocampal slices | |||||
(R,S)-ketamine | IC50 = 6.4 µM | Lumsden et al. (2019) | |||
(2R,6R)-HNK | IC50 = 63.7 µM | ||||
Inhibition of NMDAR-mediated mEPSCs, primary mouse hippocampal neurons | |||||
(R,S)-ketamine | 50 µM (∼90% inhibition) | Suzuki et al. (2017) | |||
(2R,6R)-HNK | 50 µM (∼40% inhibition) | ||||
10 µM (no inhibition) | |||||
Inhibition of NMDA-induced whole-cell current charge | |||||
(R,S)-ketamine | IC50 = 45.9 µM | Lumsden et al. (2019) | |||
(2R,6R)-HNK | IC50 > 1000 µM | ||||
(2S,6S)-HNK | IC50 > 1000 µM | ||||
Attenuation of NMDA-induced lethality in mice | |||||
(R,S)-ketamine | ED50 = 6.4 mg/kg, i.p. | Lumsden et al. (2019) | |||
(2R,6R)-HNK | ED50 = 227.8 mg/kg, i.p. | ||||
(2S,6S)-HNK | ED50 = 18.6 mg/kg, i.p. |
ND, not determined; SC-CA1, Schaffer collateral-CA1 hippocampal synapse.