MAC reduction after intrathecal coadministration of GABA(A) agonist and glutamate antagonist in rats.
OBJECTIVE
It has been reported that intrathecal coadministration of a GABA(A) agonist and a glutamate antagonist induces synergistic antinociceptive effects in rats. We hypothesized that this synergistic antinociceptive effect might induce a synergistic reduction in the minimum alveolar anesthetic concentration (MAC).


METHODS
The MAC for sevoflurane was determined before and after intrathecal administration of muscimol (GABA(A) agonist, 0.1-10 microg), AP-5 (N-methyl-D-aspartate [NMDA] antagonist, 0.1-10 microg), and YM872 (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] antagonist, 0.1-10 microg) in rats. The effects of coadministration of muscimol and AP-5 or YM872 on MAC reduction were also tested.


RESULTS
Intrathecal administration of muscimol at doses of 1 and 10 microg significantly reduced the MAC by 34.5% +/- 3.3% and 46.9% +/- 4.4%, respectively (P < 0.01). Intrathecal administration of AP-5 at a dose of 10 microg and YM872 at a dose of 10 microg significantly reduced the MAC by 25.8% +/- 2.4% and 31.4% +/- 6.3%, respectively (P < 0.01). No additional reductions in MAC values were observed when a GABA(A) agonist was combined with either an NMDA or an AMPA antagonist.


CONCLUSIONS
Intrathecal coadministration of a GABA(A) agonist and an NMDA or AMPA antagonist, which has been reported to produce a synergistic antinociceptive effect, did not induce a synergistic reduction in the MAC. The antinociceptive effect may not be the predominant factor in the reduction of the MAC induced by these drugs.
Sumikura
Hiroyuki
H
Department of Anesthesiology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-0015, Japan.
Arendt-Nielsen
Lars
L
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000032:analysis*; D000818:Animals; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008738:Methyl Ethers / Q000032:analysis*; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010146:Pain / Q000517:prevention & control; D011650:Pulmonary Alveoli / Q000737:chemistry*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D007093:Imidazoles; D008738:Methyl Ethers; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872; D009118:Muscimol; D000077149:Sevoflurane; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate