Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats.
OBJECTIVE
We studied the effects of intrathecal administration of an N-methyl-D-aspartate (NMDA) receptor antagonist and an antagonist of the glycine site of the NMDA receptor on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in rats, and on locomotor activity in conscious rats.


METHODS
In Wistar rats fitted with indwelling intrathecal catheters, we determined the MAC of isoflurane after the administration of saline (control group); the competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosponic acid(CPP) at 0.01, 0.1, and 1.0 nM; and the selective antagonist of the glycine site on the NMDA receptor complex 7-chlorokynurenic acid (7CKA) at 0.1, 1.0, and 10 nM. After measurement of MAC following administration of the antagonist, the equipotent reversal dose of NMDA or D-serine was administered. The rats were examined for the presence of locomotor dysfunction by intrathecal administration of NMDA receptor antagonists, NMDA and D-serine in conscious rats. All of the experiments were performed using randomization and masking of drugs.


RESULTS
CPP at 0.1 and 1.0 nM decreased the MAC of isoflurane by 9.9-17.6% (P < 0.05). 7CKA at 1.0 and 10 nM reduced MAC from 10.5-15.5% (P < 0.05). Intrathecal administration of NMDA or D-serine reversed the decreases in MAC to control values. Locomotor activity was not changed.


CONCLUSIONS
We believe that NMDA receptor plays an important role in determining the MAC of isoflurane in the spinal cord.
Ishizaki
K
K
Department of Anesthesiology and Reanimatology, School of Medicine, Gunma University, Japan.
Yoshida
N
N
Yoon
D M
DM
Yoon
M H
MH
Sudoh
M
M
Fujita
T
T
D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D007278:Injections, Spinal; D007530:Isoflurane / Q000493:pharmacokinetics*; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012694:Serine / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007530:Isoflurane; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid