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NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology. 1997

D T Monaghan, and H Larsen
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA. dtmonagh@unmc.edu

The potencies of various N-methyl-D-aspartate(NMDA) receptor channel blockers were determined at recombinant NMDA receptors containing differing combinations of NR1 and NR2 subunits expressed in Xenopus laevis oocytes. When the NR1 subunit was varied (NR1e/NR2A or NR1b/NR2A), none of the 9 channel blockers tested displayed a statistically different affinity. In contrast, altering NR2 composition changed the affinities of several channel blockers. Three of 10 compounds displayed significantly higher affinities for NR1b/NR2C receptors than NR1b/NR2A receptors, and three of five compounds had higher affinity at NR1b/NR2C than NR1b/NR2B receptors. Both MK-801 and N-[1-(2-thienyl)cyclohyxyl]piperidine displayed identical affinities at all receptor subunit combinations tested. However, these two compounds displayed significantly slower rates of blockade and unblockade at NR1b/NR2C than at NR1b/NR2A receptors, perhaps reflecting the shorter mean open times of NR1/NR2C receptors. NR1b/NR2B and NR1b/NR2A were distinguished by one of five compounds tested. Taken together, these results indicate that NR2 subunits impart differing pharmacological profiles to NMDA receptors; thus, it may be possible to develop NMDA receptor channel blocker antagonists of greater subtype selectivity.

UI MeSH Term Description Entries
D007473 Ion Channels Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS. Membrane Channels,Ion Channel,Ionic Channel,Ionic Channels,Membrane Channel,Channel, Ion,Channel, Ionic,Channel, Membrane,Channels, Ion,Channels, Ionic,Channels, Membrane
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009865 Oocytes Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM). Ovocytes,Oocyte,Ovocyte
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003915 Dextromethorphan Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity. d-Methorphan,Delsym,Dextromethorphan Hydrobromide,Dextromethorphan Hydrobromide, (+-)-Isomer,Dextromethorphan Hydrobromide, Monohydrate,Dextromethorphan Hydrochloride,Dextromethorphan, (+-)-Isomer,Racemethorphan,Hydrobromide, Dextromethorphan,Hydrochloride, Dextromethorphan
D005260 Female Females
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
D000081 Acetamides Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.

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