The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics.

The potency of general anesthetics from different chemical classes was tested after pretreatment with subanesthetic doses of noncompetitive N-methyl-D-aspartate (NMDA) antagonists in mice. Changes in general anesthetic potency were assessed by determination of alteration of duration of loss of righting reflex for ethanol and pentobarbital and changes in the minimum alveolar concentration (MAC) for the volatile anesthetics, halothane and diethyl ether. The ability of the noncompetitive NMDA antagonists, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine ], phencyclidine (PCP) and ketamine, to increase the potency of general anesthetics paralleled their potency as NMDA antagonists and their affinity for the PCP receptor site of the NMDA receptor-ionophore complex (MK-801 greater than PCP greater than ketamine). These results indicate that block of central NMDA receptors may contribute to the production of anesthesia by a variety of agents.