Intrathecal administration of N-methyl-D-aspartate receptor antagonist reduces the minimum alveolar anaesthetic concentration of isoflurane in rats

Abstract

We have studied the effect of intrathecal administration of N-methyl-D-aspartate (NMDA) receptor antagonists on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after administration of a competitive NMDA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 μg), a non-competitive NMDA receptor antagonist, MK801 ( 0.1, 1.0, 10, 30 μg), NMDA (0.01, 0.1, 1.0, 10, 30 μg) and saline. APV at all doses except 0.01 μg decreased MAC by 17.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 μg reduced MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did not affect MAC. Intrathecal administration of NM DA reversed these decreases in MAC, but not to control values with APV 10 and 30 μg and MK801 30 μg. We suspect that NMDA and NM DA receptor antagonists play important roles in the spinal cord in determining the MAC of isoflurane.