POTENTIATION OF MK-801-INDUCED BREATHING IMPAIRMENT BY -DIHYDROXY-6-NITRO-7-SULFAMOYL-BENZO(F)QUINOXALINE

The purpose of our study was to examine whether a significant interact ion occurs between NMDA and non-NMDA receptor antagonists on respirato ry function. For this purpose chloralose-anesthetized cats were used a nd respiratory minute volume (V-E), tidal volume (V-t) respiratory rat e (f), inspiratory and expiratory durations, and end tidal CO2 (FeCO2) were monitored. In some animals, phrenic nerve activity was also cont inuously recorded. In five spontaneously breathing animals, the NMDA r eceptor antagonist MK-801 was administered in a dose of 0.1 mg/kg i.v. , and produced decreases in V-E, V-t, f and increases in inspiratory d uration and FeCO2. Using these five animals exhibiting respiratory eff ects from prior MK-801 dosing, we then administered the non-NMDA recep tor antagonist NBQX (2, dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxal ine) i.v. in a dose of 3 mg/kg. This dose is too low to produce a neur oprotective effect in animal models of brain ischemia. In each of the five animals NBQX administration produced an immediate impairment of r espiration, culminating in apneusis within 55 s after i.v. injection. In terms of phrenic nerve discharge, inspiratory duration was increase d approximately 4-fold by MK-801, and with the addition of NBQX, conti nuous discharge of the phrenic nerve occurred. Finally, NBQX given i.v . to animals not pretreated with MK-801 had only a slight depressant e ffect on respiratory activity. These results obtained with co-administ ration of low doses of two drugs that block NMDA and non-NMDA receptor s raise the spector that combined use of these agents to ameliorate di sorders in neurological function may be extremely deleterious to respi ratory function.