Lack of effect of L-687,414 ((+)-cis-4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology.

摘要

1. N-methyl-D-aspartate (NMDA) receptor ion channel antagonists have been reported to cause pronounced increases in cerebral glucose metabolism (CMRglc) and transient reversible vacuolation within pyramidal cortical neurones. The present studies examined in rats the effects of the NMDA receptor antagonist, L-687,414 (R-(+)-cis-4-methyl-3-amino-l-hydroxypyrolid-2-one (+)-cis-4-methyl-HA-966) on regional CMRglc and cortical neuronal morphology. 2. L-687,414 was given as a steady state intravenous infusion for 4 h in a neuroprotective dose regime of 17.5 mg free base kg-1 bolus followed by 225 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 35 mg kg-1 bolus followed by 440 micrograms kg-1 min-1 (n = 10). Data were compared to a parallel series of experiments in rats given the NMDA receptor ion channel antagonist, dizocilpine for 4 h in the optimum intravenous neuroprotective dose-regime of 0.12 mg kg-1 bolus followed by 1.8 micrograms kg-1 min-1 (n = 8) or at the higher dose rate of 0.4 mg kg-1 bolus followed by 6 micrograms kg-1 min-1 (n = 4; morphology only studied). A saline-infused group of rats (n = 8) were used as controls. 3. CMRglc was studied by use of [14C]-2-deoxyglucose and autoradiography (n = 4 each group) whilst plasma drug levels were in a steady state during the final 45 min of the 4 h drug infusion.(ABSTRACT TRUNCATED AT 250 WORDS)