title: Differential influence of 7 cations on 16 non-competitive NMDA receptor blockers.
abstract: The specific binding of the NMDA receptor (NR) channel ligand [(3)H]MK-801 to rat brain membranes is sensitive to positively charged buffer ingredients as to tris(hydroxymethyl)aminomethane (Tris), to Na(+), or to protons. Here we demonstrate that 16 non-competitive NR antagonists, including 5 long-chain diamines, classical NR channel blockers and several less known compounds, differ widely in their sensitivities to cationic buffer constituents. Although chemically distinguished either as extended di-cationic or as compact mono-cationic, their sensitivities to cationic buffer ingredients did not suggest this grouping. While the di-cationic compounds are known for their sensitivity to spermine (polyamine inverse agonists), also some of the mono-cationic blockers exhibited this feature. They might share as common target a recently described negatively charged extracellular GluN1/GluN2B interface.
authors: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Austria.
authors: Michael L
authors: ML
authors: Berger
authors: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Austria.
authors: Patrick
authors: P
authors: Rebernik
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000737:chemistry / Q000494:pharmacology*; D003959:Diamines / Q000737:chemistry / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002412:Cations; D003959:Diamines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: Magnesium; NMDA receptor; Polyamines; Potassium; Sodium; [(3)H]MK-801