Biomaterial Database

Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics. 2006

Ken Solt, and Edmond I Eger, and Douglas E Raines

Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. ksolt@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.

UI	MeSH Term	Description	Entries
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014982	Xenopus laevis	The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.	Platanna,X. laevis,Platannas,X. laevi
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D018681	Anesthetics, General	Agents that induce various degrees of analgesia; depression of consciousness, circulation, and respiration; relaxation of skeletal muscle; reduction of reflex activity; and amnesia. There are two types of general anesthetics, inhalation and intravenous. With either type, the arterial concentration of drug required to induce anesthesia varies with the condition of the patient, the desired depth of anesthesia, and the concomitant use of other drugs. (From AMA Drug Evaluations Annual, 1994, p.173)	General Anesthetic,General Anesthetics,Anesthetic, General
D018690	Excitatory Amino Acid Agonists	Drugs that bind to and activate excitatory amino acid receptors.	Amino Acids, Excitatory, Agonists,Glutamate Agonists,Agonists, Excitatory Amino Acid,Amino Acid Agonist, Excitatory,Amino Acid Agonists, Excitatory,EAA Agonist,EAA Agonists,Excitatory Amino Acid Agonist,Glutamate Agonist,Agonist, EAA,Agonist, Glutamate,Agonists, EAA,Agonists, Glutamate
D018691	Excitatory Amino Acid Antagonists	Drugs that bind to but do not activate excitatory amino acid receptors, thereby blocking the actions of agonists.	Amino Acids, Excitatory, Antagonists,Excitatory Amino Acid Antagonist,Glutamate Antagonist,Glutamate Antagonists,Glutamate Receptor Antagonist,Amino Acid Antagonists, Excitatory,Antagonists, Excitatory Amino Acid,EAA Antagonists,Glutamate Receptor Antagonists,Antagonist, Glutamate,Antagonist, Glutamate Receptor,Antagonists, EAA,Antagonists, Glutamate,Antagonists, Glutamate Receptor,Receptor Antagonist, Glutamate,Receptor Antagonists, Glutamate