EFFECT OF CGS-19755, A COMPETITIVE N-METHYL-D-ASPARTATE ANTAGONIST, ON GENERAL ANESTHETIC POTENCY

CGS 19755 is a competitive N-methyl-D-aspartate (NMDA) receptor antagonist which penetrates the blood-brain barrier. The effect of pretreatment with subanesthetic doses of CGS 19755 on general anesthetic potency was determined in mice. Mice were pretreated with saline or CGS 19755 by intraperitoneal (IP) administration 30 min before IP administration of an anesthetic dose of ethanol or pentobarbital or measurement of the volatile anesthetic minimum alveolar concentration (MAC). CGS 19755 increased the duration of ethanol- and pentobarbital-induced loss of righting reflex in a dose-dependent manner. The highest dose of CGS 19755 tested, 50 mg/kg, increased duration of loss of righting reflex by about four- and twofold for ethanol and pentobarbital, respectively. CGS 19755 also decreased the MAC for halothane. However, CGS 19755 pretreatment had no effect on the MAC for diethyl ether. These results suggest that the potency of certain general anesthetic agents can be increased by antagonism of brain NMDA receptors.