Respiratory effects of halothane and AMPA receptor antagonist synergy in rats.
The influence of N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonists in combination with halothane anaesthesia on the respiratory system was investigated. Under 1.5% halothane anaesthesia, respiratory parameters including respiratory rate, minute volume, tidal volume, inspiratory and expiratory duration were measured before and after drug administration in rats. The AMPA receptor antagonists, 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione hydrochloride, YM90K (5 and 10 mg/kg) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX, 15 mg/kg), which were administered intravenously for 30 min, significantly reduced the respiratory rate (P < 0.01) and minute volume (P < 0.01) and increased the tidal volume (P < 0.05) compared with values obtained before drug administration. None of these drugs affected respiratory parameters in the absence of anaesthesia. A NMDA receptor antagonist, MK-801 (0.5 mg/kg), which was administered intravenously for 30 min, also significantly reduced respiratory rate (P < 0.01), minute volume (P < 0.01) and tidal volume (P < 0.01) and prolonged inspiratory duration (P < 0.05). These results suggest that both AMPA and NMDA receptor antagonists cause respiratory depression under halothane anaesthesia in rats, although the mechanisms may be different for the two types of antagonists.
Shimazu
Y
Y
Department of Pharmacology, School of Medicine, Hamamatsu University, Japan.
Umemura
K
K
Kawano
K
K
Hokamura
K
K
Kawazura
H
H
Nakashima
M
M
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D015656:Respiratory Mechanics / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D006221:Halothane