Use-dependent pentobarbital block of kainate and quisqualate currents

Pentobarbitone modulation of NMDA receptors in neurones isolated from the rat olfactory brain

“…Use-dependent local anaesthetic blockade of open voltage-gated sodium channels operates in a similar way (Butterworth & Strichartz, 1990). Marszalec & Narahashi (1993) have shown that pentobarbitone apparently induces a similar use-dependent block of kainate/AMPA channels.…”

“…The depression of inward current was not associated with any consistent change in the current-voltage relationship but pentobarbitone appeared to increase the rate at which the NMDA receptors desensitize. The failure of other groups to find similar sensitivity is difficult to explain (see Cai & McCaslin, 1993;Marszalec & Narahashi, 1993). It has been shown, however, that heteromeric recombinant NMDA receptors assembled from different subunits have distinct pharmacological properties (Kutsuwada et al, 1992;Monyer et al, 1992).…”

Inhibition of learning and memory by general anesthetics

“…[120][121][122] Unlike GABA A receptors and NMDA receptors, the AMPA and kainite subtypes of glutamate receptors are not key targets for most general anesthetics, 65,106 although barbiturates inhibit AMPA and kainate receptors. [123][124][125] Intravenous anesthetics, including etomidate, propofol, and barbiturates, enhance the GABA A receptor function, and this effect contributes to hypnosis, immobility, and memory blockade. 105,108,111,114,126,127 The halogenated volatile anesthetics (isoflurane, sevoflurane, and desflurane) also enhance GABA A receptor function, although these drugs appear to be less selective for GABA A receptors than most intravenous anesthetics.…”

The sensitivity of AMPA‐selective glutamate receptor channels to pentobarbital is determined by a single amino acid residue of the α2 subunit

“…The ~2 subunit also appears to be important with respect to its contribution to the pentobarbital sensitivity of native AMPA receptor channels because the ICs0 value for the pentobarbital inhibition of kainate currents in cultured cortical neurons (50/aM) [4] is similar to that of the ~1/~2 heteromeric channel (~45/aM). The anesthetic ECs0 (plasma concentration to prevent movement of 50% of patients in response to a painful stimulus) value for pentobarbital is ~ 50/aM [1].…”

“…For example, the sensitivity of cortical neurons to L-glutamate was depressed by barbiturates [2]. Furthermore, pentobarbital block of kainate currents in cultured mouse hippocampal neurons was shown to be voltagedependent [3] and that of kainate and quisqualate currents in cultured rat cortical neurons was use-dependent [4]. These observations suggest the channel block mechanisms of barbiturates action to inhibit the glutamate receptor (GluR) channels.…”