[Actions of ketamine not related to NMDA and opiate receptors].
In recent years, much interest has focused on NMDA- and opiate-receptor-mediated actions of ketamine, whereas the search for other potential neuronal effects of this phencyclidine derivative has not attracted comparable attention. Nevertheless, the superfamily of voltage-operated membrane channels (VOC), ligand-operated ion channels (LOC) stimulated by acetylcholine and GABA, the non-NMDA subtypes of glutamate-activated LOC (kainate and AMPA receptor channels) and the closely related re-uptake processes of the monoamines noradrenaline, dopamine and serotonin should be considered potential targets of ketamine within the nervous system. Therefore, this review article summarizes our current knowledge of ketamine effects on these transmembrane ion channels and carrier mechanisms in the neuron. Unlike the NMDA-insensitive glutamate receptors for kainate and AMPA, the LOC activated by acetylcholine and the principal inhibitory amino acid GABA (gamma-aminobutyric acid) were both sensitive to clinical concentrations of ketamine, although in different ways. The relevance of these findings for the generation of the anaesthetic state, however, still remains to be established. Moreover, all VOC tested so far were reversibly inhibited at supra-clinical concentrations of ketamine (> 100 microM). Whereas no direct relevance to the state of general anaesthesia emerges from these data, local anaesthesia produced by comparably high concentrations of ketamine can be explained on the basis of its more or less unspecific inhibitory actions on VOC. Finally, the excellent antinociceptive activity of ketamine at the spinal and supra-spinal level may result at least in part from its inhibitory effects on the neuronal uptake of the monoamines noradrenaline, dopamine and serotonin.
Abteilung für Allgemeine Anaesthesie und Intensivmedizin (B) der Universität Wien.
H G
HG
Kress
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007649:Ketamine / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects
D000777:Anesthetics; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D007649:Ketamine
NMDA- und Opiatrezeptor-unabhängige Wirkungen von Ketamin.