Comparative patch-clamp studies with freshly dissociated rat hippocampal and striatal neurons on the NMDA receptor antagonistic effects of amantadine and memantine. 1996

C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
Department of Pharmacology, Merz and Co., Frankfurt am Main, Germany.

Patch- and concentration-clamp techniques were used to compare the effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists (+)-MK-801 (dizocilpine, (+)-5-methyl-10, 11-dihydro-5H-dibenzocyclohepten-5, 10-imine maleate), ketamine, memantine (1-amino-3,5-dimethyladamantane) and amantadine (1-amino-adamantane) on agonist-induced inward currents in freshly dissociated rat hippocampal and striatal neurons. In hippocampal neurons, ketamine (5 microM), menantine (10 microM) and amantadine (100 microM) selectively antagonized inward current responses to NMDA (500 microM plus glycine 5 microM) in a voltage-dependent manner without affecting responses to (s)-alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (100 microM) or gamma-aminobutyric acid (10 microM). The NMDA receptor antagonistic effect of all four agents was typical of open channel blockade. The kinetics of blockade/unblockade was inversely related to antagonist affinity. In hippocampal neurons amantadine was the least potent NMDA receptor antagonist (IC50 18.6 +/- 0.9 microM) and showed the fastest blocking kinetics, whereas (+)-MK-801 was the most potent (IC50 0.12 +/- 0.01 microM) and showed the slowest blocking kinetics. Memantine (IC50 1.04 +/- 0.26 microM) and ketamine (IC50 0.43 +/- 0.10 microM) were almost equipotent and had similar, intermediate blocking kinetics. In striatal neurons recorded under identical conditions (+)-MK-801, ketamine and memantine were 3- to 4-fold less potent whereas amantadine was somewhat more potent than on hippocampal neurons. This could offer an explanation for the better clinical profile of amantadine in Parkinson's disease, as therapeutically relevant concentrations of amantadine are likely to be more active in the striatum whereas memantine is likely to be more active in other structures.

UI MeSH Term Description Entries
D007649 Ketamine A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors. 2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone,CI-581,Calipsol,Calypsol,Kalipsol,Ketalar,Ketamine Hydrochloride,Ketanest,Ketaset,CI 581,CI581
D008559 Memantine AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. 1,3-Dimethyl-5-aminoadamantane,1-Amino-3,5-dimethyladamantane,Axura,D-145,D145,Ebixa,Memantin,Memantine Hydrochloride,Namenda,D 145
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000547 Amantadine An antiviral that is used in the prophylactic or symptomatic treatment of influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. 1-Aminoadamantane,Adamantylamine,Adekin,Aman,Amanta,Amanta-HCI-AZU,Amanta-Sulfate-AZU,Amantadin AL,Amantadin AZU,Amantadin Stada,Amantadin-neuraxpharm,Amantadin-ratiopharm,Amantadina Juventus,Amantadina Llorente,Amantadine Hydrochloride,Amantadine Sulfate,Amixx,Cerebramed,Endantadine,Gen-Amantadine,Infecto-Flu,Infex,Mantadix,Midantan,PMS-Amantadine,Symadine,Symmetrel,Viregyt,Wiregyt,tregor,1 Aminoadamantane,AL, Amantadin,AZU, Amantadin,Amanta HCI AZU,Amanta Sulfate AZU,AmantaHCIAZU,AmantaSulfateAZU,Amantadin neuraxpharm,Amantadin ratiopharm,Amantadinneuraxpharm,Amantadinratiopharm,Gen Amantadine,GenAmantadine,Hydrochloride, Amantadine,Infecto Flu,InfectoFlu,Juventus, Amantadina,Llorente, Amantadina,PMS Amantadine,PMSAmantadine,Stada, Amantadin,Sulfate, Amantadine
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
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
D016202 N-Methylaspartate An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA). N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats

Related Publications

C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
October 1998, The Journal of physiology,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
October 1991, Brain research,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
August 2005, Brain research,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
January 1994, Journal of neural transmission. Supplementum,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
October 2010, Journal of neural transmission (Vienna, Austria : 1996),
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
February 1998, Chemical senses,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
July 1990, Neuroscience letters,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
July 1987, The Journal of general physiology,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
April 2006, Brain research,
C G Parsons, and V A Panchenko, and V O Pinchenko, and A Y Tsyndrenko, and O A Krishtal
September 1995, Journal of neurophysiology,
Copied contents to your clipboard!