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ANESTHETIC PHARMACOLOGY

Differential Modulation of Human N-Methyl-d-Aspartate Receptors by Structurally Diverse General Anesthetics

Ken Solt, MD^*, Edmond I. Eger, II, MD, and Douglas E. Raines, MD^*

*Department of Anesthesia and Critical Care, Massachusetts General Hospital, and Department of Anaesthesia, Harvard Medical School, Boston Massachusetts; and Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence and reprint requests to Ken Solt, MD, Dept. of Anesthesia and Critical Care, Massachusetts General Hospital, 55 Fruit Street, Edwards 505, Boston, MA 02114. Address e-mail to: ksolt{at}partners.org

N-Methyl-d-aspartate (NMDA) receptors have a presumed role in excitatory synaptic transmission and nociceptive pathways. Although previous studies have found that inhaled anesthetics inhibit NMDA receptor-mediated currents at clinically relevant concentrations, the use of different experimental protocols, receptor subtypes, and/or tissue sources confounds quantitative comparisons of the NMDA receptor inhibitory potencies of inhaled anesthetics. In the present study, we sought to fill this void by defining, using the two-electrode voltage-clamp technique, the extent to which diverse clinical and aromatic inhaled anesthetics inhibit the NR1/NR2B subtype of the human NMDA receptor expressed in Xenopus laevis oocytes. At 1 minimum alveolar anesthetic concentration (MAC), anesthetic compounds reversibly inhibited NMDA receptor currents by 12 ± 6% to 74 ± 6%. These results demonstrate that equianesthetic concentrations of inhaled anesthetics can differ considerably in the extent to which they inhibit NMDA receptors. Such differences may be useful for defining the role that this receptor plays in producing the in vivo actions of general anesthetics.

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