The anesthetic interaction between adenosine triphosphate and N-methyl-D-aspartate receptor antagonists in the rat.
Modulation of synaptic neurotransmission through the ligand-gated ion channel is probably involved in the mechanisms of analgesic and anesthetic actions. In the central nervous system, adenosine triphosphate and glutamate are fast excitatory neurotransmitters through their effects on P2X and N-methyl-D-aspartate (NMDA) receptors respectively. To examine the anesthetic interaction between adenosine triphosphate and NMDA receptor antagonists, we studied the effect of intracerebroventricular administration of P2 and/or NMDA antagonists on the minimum alveolar concentration (MAC) of sevoflurane in rats. Intracerebro- ventricular administration of phosphonopentanoic acid azophenyl-2',4'-disulfonate and D (-)-2-anino-5-phophonopentanoic acid, P2 and NMDA antagonists, significantly reduced the MAC of sevoflurane. The reduction of the MAC by both phosphonopentanoic acid azophenyl-2',4'-disulfonate and D (-)-2-anino-5-phophonopentanoic acid was dose-dependent. The effect of coadministration of both antagonists was additive in the reduction of sevoflurane minimum alveolar concentration. These results suggest that P2 and NMDA receptors mediate nociceptive/anesthetic processing as inhibition of these receptors resulted in analgesic and anesthetic effects. However the pathway mediated through each receptor may be different postsynaptically and/or one of these presynaptic receptors may modulate the neurotransmitter release of the other.
Masaki
E
E
Department of Pharmacology (I), Jikei University School of Medicine, Tokyo 105-8461, Japan. jkyakuri@sepia.ocn.ne.jp
Yamazaki
K
K
Ohno
Y
Y
Nishi
H
H
Matsumoto
Y
Y
Kawamura
M
M
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008738:Methyl Ethers / Q000493:pharmacokinetics*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D000077149:Sevoflurane; D013237:Stereoisomerism
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D008738:Methyl Ethers; D058919:Purinergic P2 Receptor Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D000077149:Sevoflurane; D011732:Pyridoxal Phosphate; D015763:2-Amino-5-phosphonovalerate