NEURONAL ACTIONS OF KETAMINE NOT MEDIATED BY NMDA OR OPIATE RECEPTORS

In recent years, much interest has focused on NMDA- and opiate-recepto r-mediated actions of ketamine, whereas the search for other potential neuronal effects of this phencyclidine derivative has not attracted c omparable attention. Nevertheless, the superfamily of voltage-operated membrane channels (VOC), ligand-operated ion channels (LOC) stimulate d by acetylcholine and GABA, the non-NMDA subtypes of glutamate-activa ted LOC (kainate and AMPA receptor channels) and the closely related r e-uptake processes of the monoamines noradrenaline, dopamine and serot onin should be considered potential targets of ketamine within the ner vous system. Therefore, this review article summarizes our current kno wledge of ketamine effects on these transmembrane ion channels and car rier mechanisms in the neuron. Unlike the NMDA-insensitive glutamate r eceptors for kainate and AMPA, the LOC activated by acetylcholine and the principal inhibitory amino acid GABA (gamma-aminobutyric acid) wer e both sensitive to clinical concentrations of ketamine, although in d ifferent ways. The relevance of these findings for the generation of t he anaesthetic state, however, still remains to be established. Moreov er, all VOC tested so far were revesibly inhibited at supra-clinical c oncentrations of ketamine (> 100 muM). Whereas no direct relevance to the state of general anaesthesia emerges from these data, local anaest hesia produced by comparably high concentrations of ketamine can be ex plained on the basis of its more or less unspecific inhibitory actions on VOC. Finally, the excellent antinociceptive activity of ketamine a t the spinal and supra-spinal level may result at least in part from i ts inhibitory effects on the neuronal uptake of the monoamines noradre naline, dopamine and serotonin.