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Plazas, P.V.; Savino, J.; Kracun, S.; Gomez-Casati, M.E.; Katz, E.; Parsons, C.G.; Millar, N.S.; Elgoyhen, A.B. "Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors" (2007) European Journal of Pharmacology. 566(1-3):11-19
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Abstract:

In this study we report the effects of neramexane, a novel amino-alkyl-cyclohexane derivative that is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, on recombinant rat α9α10 nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes. We compared its effects with those of memantine, a well-studied pore blocker of NMDA receptors, currently used in therapeutics for the treatment of Alzheimer's disease. Our results indicate that both compounds block acetylcholine-evoked responses at micromolar concentrations with a rank order of potency of neramexane > memantine, P < 0.05. Block by neramexane of acetylcholine responses was not overcome at high concentrations of the agonist, indicative of a non-competitive inhibition. The lack of interaction of neramexane with the ligand binding domain was confirmed by radioligand binding experiments in transfected tsA201 cells. Moreover, block did not involve an increase in desensitization kinetics, it was independent of the resting potential of the membrane at low concentrations of neramexane and slightly voltage-dependent at concentrations higher than 1 μM. Finally, clinically-relevant concentrations of neramexane blocked native α9α10-containing nicotinic acetylcholine receptors of rat inner hair cells, thus demonstrating a possible in vivo relevance in potentially unexplored therapeutic areas. © 2007 Elsevier B.V. All rights reserved.

Registro:

Documento: Artículo
Título:Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors
Autor:Plazas, P.V.; Savino, J.; Kracun, S.; Gomez-Casati, M.E.; Katz, E.; Parsons, C.G.; Millar, N.S.; Elgoyhen, A.B.
Filiación:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina
Departamento de Fisiología, Biología Molecular y Celular, FCEyN, Universidad de Buenos Aires, Argentina
Departamento de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Argentina
Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany
Department of Pharmacology, University College London, London, United Kingdom
Palabras clave:Acetylcholine; Hair cells; N-methyl-d-aspartate receptor antagonist; Neramexane; Nicotinic acetylcholine receptors; cyclohexane derivative; memantine; n methyl dextro aspartic acid receptor blocking agent; neramexane; nicotinic receptor; radioligand; acetylcholine; cyclopentane derivative; memantine; n methyl dextro aspartic acid receptor; neramexane; nicotinic receptor; nicotinic receptor blocking agent; protein subunit; recombinant protein; Alzheimer disease; article; cell membrane potential; controlled study; desensitization; drug binding; drug inhibition; drug potency; drug protein binding; embryo; genetic transfection; hair cell; human; human cell; in vivo study; kinetics; nonhuman; oocyte; priority journal; protein expression; rat; Xenopus laevis; animal; cell line; drug antagonism; drug effect; genetics; hair cell; metabolism; physiology; Sprague Dawley rat; Acetylcholine; Animals; Cell Line; Cyclopentanes; Hair Cells, Inner; Humans; Memantine; Nicotinic Antagonists; Oocytes; Protein Subunits; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Receptors, Nicotinic; Recombinant Proteins; Xenopus laevis
Año:2007
Volumen:566
Número:1-3
Página de inicio:11
Página de fin:19
DOI: http://dx.doi.org/10.1016/j.ejphar.2007.03.026
Título revista:European Journal of Pharmacology
Título revista abreviado:Eur. J. Pharmacol.
ISSN:00142999
CODEN:EJPHA
CAS:memantine, 19982-08-2, 41100-52-1; neramexane, 209185-99-9, 219810-59-0, 457068-92-7; acetylcholine, 51-84-3, 60-31-1, 66-23-9; Acetylcholine, 51-84-3; Cyclopentanes; Memantine, 19982-08-2; MRZ 2579; Nicotinic Antagonists; Protein Subunits; Receptors, N-Methyl-D-Aspartate; Receptors, Nicotinic; Recombinant Proteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142999_v566_n1-3_p11_Plazas

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Citas:

---------- APA ----------
Plazas, P.V., Savino, J., Kracun, S., Gomez-Casati, M.E., Katz, E., Parsons, C.G., Millar, N.S.,..., Elgoyhen, A.B. (2007) . Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors. European Journal of Pharmacology, 566(1-3), 11-19.
http://dx.doi.org/10.1016/j.ejphar.2007.03.026
---------- CHICAGO ----------
Plazas, P.V., Savino, J., Kracun, S., Gomez-Casati, M.E., Katz, E., Parsons, C.G., et al. "Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors" . European Journal of Pharmacology 566, no. 1-3 (2007) : 11-19.
http://dx.doi.org/10.1016/j.ejphar.2007.03.026
---------- MLA ----------
Plazas, P.V., Savino, J., Kracun, S., Gomez-Casati, M.E., Katz, E., Parsons, C.G., et al. "Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors" . European Journal of Pharmacology, vol. 566, no. 1-3, 2007, pp. 11-19.
http://dx.doi.org/10.1016/j.ejphar.2007.03.026
---------- VANCOUVER ----------
Plazas, P.V., Savino, J., Kracun, S., Gomez-Casati, M.E., Katz, E., Parsons, C.G., et al. Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors. Eur. J. Pharmacol. 2007;566(1-3):11-19.
http://dx.doi.org/10.1016/j.ejphar.2007.03.026