Neuroprotective Doses of N-Methyl-D-Aspartate Receptor Antagonists Profoundly Reduce the Minimum Alveolar Anesthetic Concentration (MAC) for Isoflurane in Rats

Abstract

N-methyl-D-aspartate (NMDA) receptor antagonists, which block one of the glutamate receptors, have provided evidence of cerebral protection in animal models of focal cerebral ischemia. We examined the effect of neuroprotective doses of one noncompetitive (dizocilpine) and two competitive (D-CPP-ene, CGS 19755) NMDA antagonists on the minimum alveolar anesthetic concentration (MAC) of isoflurane in rats. A single bolus injection of any of the three NMDA antagonists produced a significant (P < 0.01) and sustained (> 3 h) decrease in the MAC of isoflurane. Dizocilpine decreased MAC by 33%-38% at a dose of 0.15 mg/kg and 48%-54% at a dose of 0.5 mg/kg. D-CPP-ene decreased MAC by 32%-37% at a dose of 1.5 mg/kg and 39%-45% at a dose of 4.5 mg/kg. CGS 19755 decreased MAC by 19%-24% at a dose of 3 mg/kg and 49%-58% at a dose of 10 mg/kg. Dizocilpine, but not the competitive antagonists, produced a small transient decrease in mean arterial blood pressure. The sustained anesthetic potency of neuroprotective doses of NMDA antagonists supports the idea that glutaminergic receptor activity is involved in determining the anesthetic state.

Differential actions of isoflurane and ketamine-based anaesthetics on cochlear function in the mouse

“…In vitro studies have shown that isoflurane potentiates glycine receptor (GlyR) currents (Downie et al, 1996; Harrison et al, 1993; Mascia et al, 1996), the GABA receptor (GABAR) (Harrison et al, 1993; Lin et al, 1993; Mihic et al, 1994) and the glutamate-selective kainate receptor (Dildy-Mayfield et al, 1996; Minami et al, 1998), while inhibiting the nicotinic acetylcholine receptor (nAChR) (Forman and Raines, 1998). Studies have also demonstrated that isoflurane has an effect on the N-methyl-D-aspartate (NMDA) receptor (de Sousa et al, 2000; Franks, 2008; Ishizaki et al, 1995; Kuroda et al, 1993; Martin et al, 1995). On the other hand, ketamine does not affect the GlyR or the GABAR (Yamakura et al, 2000, 2001a) and only has a small inhibitory effect on the nAChR (Wachtel and Wegrzynowicz, 1992).…”

Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility?

“…Blockade of NMDA receptors, can markedly decrease MAC 129,144,145. Ketamine, which largely produces anesthesia by inhibiting NMDA receptor function [but also acts on acetylcholine receptors],146 can abolish movement in response to noxious stimulation.…”

MAC reduction after intrathecal coadministration of GABA A agonist and glutamate antagonist in rats

“…Throughout the experiments, the oxygen supply to the sevoflurane vaporizer was kept at 2 l·min Ϫ1 . The end-tidal concentrations of sevoflurane and CO 2 were monitored (sampling rate, 200 ml·min Ϫ1 ) by an anesthetic gas monitor (M1025B, Hewlett Packard) [15]. The end-tidal CO 2 level was maintained between 35 and 45 mmHg by adjusting the respiratory rate.…”