This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Masaki, E. Articles by Kawamura, M. Search for Related Content PubMed PubMed Citation Articles by Masaki, E. Articles by Kawamura, M. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

The Anesthetic Interaction Between Adenosine Triphosphate and N-methyl-D-Aspartate Receptor Antagonists in the Rat

Eiji Masaki, MD, PhD^*,, Koji Yamazaki, MD, Yuji Ohno, MD^*, Haruhisa Nishi, PhD^*, Yasunori Matsumoto, DDS^*, and Masahiro Kawamura, MD^*

Departments of *Pharmacology (I), Anesthesiology, and Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan

Address correspondence and reprint requests to Eiji Masaki, Department of Pharmacology (I), Jikei University School of Medicine, 3–25-8, Nishishinbashi Minato-ku, Tokyo 105-8461, Japan. Address e-mail to jkyakuri{at}sepia.ocn.ne.jp

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.

Implications: Because P2X and N-methyl-D-aspartate receptors mediate a fast neurotransmission, we examined the anesthetic interaction between antagonists of these receptors. P2 and N-methyl-D-aspartate receptor antagonists showed additive anesthetic interaction.

This article has been cited by other articles:

				E. I. Eger II, M. Liao, M. J. Laster, A. Won, J. Popovich, D. E. Raines, K. Solt, R. C. Dutton, F. V. Cobos II, and J. M. Sonner Contrasting Roles of the N-Methyl-d-Aspartate Receptor in the Production of Immobilization by Conventional and Aromatic Anesthetics. Anesth. Analg., May 1, 2006; 102(5): 1397 - 1406. [Abstract] [Full Text] [PDF]

				E. Masaki, M. Kawamura, and F. Kato Attenuation of Gap-Junction-Mediated Signaling Facilitated Anesthetic Effect of Sevoflurane in the Central Nervous System of Rats Anesth. Analg., March 1, 2004; 98(3): 647 - 652. [Abstract] [Full Text] [PDF]

				J. M. Sonner, J. F. Antognini, R. C. Dutton, P. Flood, A. T. Gray, R. A. Harris, G. E. Homanics, J. Kendig, B. Orser, D. E. Raines, et al. Inhaled Anesthetics and Immobility: Mechanisms, Mysteries, and Minimum Alveolar Anesthetic Concentration Anesth. Analg., September 1, 2003; 97(3): 718 - 740. [Abstract] [Full Text] [PDF]

				C. Stabernack, J. M. Sonner, M. Laster, Y. Zhang, Y. Xing, M. Sharma, and E. I. Eger II Spinal N-Methyl-D-Aspartate Receptors May Contribute to the Immobilizing Action of Isoflurane Anesth. Analg., January 1, 2003; 96(1): 102 - 107. [Abstract] [Full Text] [PDF]