INTRATHECAL ADMINISTRATION OF N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST REDUCES THE MINIMUM ALVEOLAR ANESTHETIC CONCENTRATION OF ISOFLURANE IN RATS

We have studied the effect of intrathecal administration of N-methyl-D -aspartate (NMDA) receptor antagonists on the minimum alveolar anaesth etic concentration (MAC) of isoflurane in rats. In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflu rane after administration of a competitive NM DA receptor antagonist, APV (0.01, 0.1, 1.0, 10, 30 mu g), a non-competitive NMDA receptor ant agonist, MK801. (0.1, 1.0, 10, 30 mu g), NMDA (0.01, 0.1, 1.0, 10, 30 mu g) and saline. APV at all doses except 0.01 mu g decreased MAC by 1 7.1-32% (P < 0.001 and P < 0.0001). Although MK801 at 10 and 30 mu g r educed MAC by 24.3-31.7% (P < 0.001 and P < 0.0001), lower doses did n ot affect MAC. Intrathecal administration of NMDA reversed these decre ases in MAC, but not to control values with APV 10 and 30 mu g and MK8 01 30 mu g. We suspect that NMDA and NM DA receptor antagonists play i mportant roles in the spinal cord in determining the MAC of isoflurane .