Ketamine acts as a non-competitive N-methyl-D-aspartate antagonist on frog spinal cord in vitro.

The effects of the dissociative anaesthetic, ketamine, the divalent cation, magnesium and the organic antagonist, 2-amino-5-phosphonovalerate (APV), were examined on responses of motoneurones to excitatory amino acids in the hemisected spinal cord of the frog in vitro. The amino acids, N-methyl-D-aspartate (NMDA), kainate and quisqualate, produced dose-dependent depolarizations. Ketamine, magnesium and APV depressed responses to NMDA but had no effect on those to quisqualate and kainate. Magnesium and APV produced Schild plot slopes that were not different from unity, whereas ketamine had a slope significantly less than unity, indicative of a non-competitive action. Experiments in which combinations of drugs were tested indicated that these substances act by three distinct mechanisms to cause antagonism of the actions of NMDA.