Differential effects of ketamine enantiomers on NMDA receptor currents in cultured neurons.
The effects of R- and S-ketamine on N-methyl-D-aspartate receptor-activated cation currents (NMDA receptor currents) of voltage-clamped cultured rat hippocampal neurons were investigated using the whole-cell patch-clamp technique. Both enantiomers exhibited a voltage- and use-dependent blockade of NMDA receptor currents, with the S-enantiomer being about twice as potent as the R-enantiomer. Calculated relative forward and backward rates suggest that conformational differences influence the dissociation from the binding site more than the association with it.
Zeilhofer
H U
HU
Max-Planck-Institut fuer Biophysikalische Chemie, Karl-Friedrich-Bonhoeffer-Institut, Goettingen, Germany.
Swandulla
D
D
Geisslinger
G
G
Brune
K
K
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism
D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine