The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate

TLDR

The study examined how ketamine and phencyclidine affect spinal neuron responses to amino acids and acetylcholine in decerebrate or pentobarbitone‑anaesthetized cats and rats, using electrophoretic administration. Ketamine and phencyclidine selectively block NMDA‑mediated excitation while sparing responses to quisqualate, kainate, and to a lesser extent, acetylcholine, with greater inhibition of dorsal root‑evoked synaptic excitation, and intravenous doses similarly reduce NMDA‑mediated responses, suggesting NMDA receptor blockade underlies their anesthetic/analgesic effects.

Abstract

The interaction of two dissociative anaesthetics, ketamine and phencyclidine, with the responses of spinal neurones to the electrophoretic administration of amino acids and acetylcholine was studied in decerebrate or pentobarbitone‐anaesthetized cats and rats. Both ketamine and phencyclidine selectively blocked excitation by N‐methyl‐aspartate (NMA) with little effect on excitation by quisqualate and kainate. Ketamine reduced responses to L‐aspartate somewhat more than those of l ‐glutamate; the sensitivity of responses to these two putative transmitters was between that to NMA on one hand and that to quisqualate or kainate on the other. On Renshaw cells, ketamine and phencyclidine reduced responses to acetylcholine less than those to NMA but more than those to quisqualate or kainate. Dorsal root‐evoked synaptic excitation of Renshaw cells was reduced to a greater extent than that following ventral root excitation. Intravenous ketamine, 2.5–20 mg/kg, and phencyclidine, 0.2–0.5 mg/kg, also selectively blocked excitation of neurones by NMA. Ketamine showed no consistent or selective effect on inhibition of spinal neurones by electrophoretically administered glycine or γ‐aminobutyricacid (GABA). The results suggest that reduction of synaptic excitation mediated via NMA receptors contributes to the anaesthetic/analgesic properties of these two dissociative anaesthetics.