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LOS ANTAGONISTAS DE LOS RECEPTORES NMDA PARA LA FARMACOTERAPIA DEL ALCOHOLISMO

LOS ANTAGONISTAS DE LOS RECEPTORES NMDA PARA LA FARMACOTERAPIA DEL ALCOHOLISMO

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Los mecanismos mediados por los receptores NMDA desempeñan un papel central en la aparición de dependencia y abstinencia del alcohol. En consecuencia, pueden ser blancos útiles de las drogas utilizadas para el tratamiento del alcoholismo. Existen nuevos antagonistas no competitivos del receptor NMDA con un perfil aceptable de efectos adversos que son drogas candidatas potenciales para tratar la dependencia del alcohol ya que atenúan los síntomas físicos y los componentes afectivos de la abstinencia.
Autor:
József Nagy
Columnista Experto de SIIC
Artículos publicados por József Nagy
Recepción del artículo
26 de Noviembre, 2006
Aprobación
15 de Diciembre, 2006
Primera edición
11 de Junio, 2007
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
El consumo de alcohol a largo plazo resulta en la aparición de dependencia como consecuencia de cambios del funcionamiento de neurotransmisores específicos. Los datos reunidos sugieren que los receptores glutamatérgicos ionotrópicos tipo N-metil-d-aspartato (NMDA) son un sitio de acción del etanol especialmente importante. El etanol inhibe con potencia los receptores NMDA y la exposición prolongada a dicha sustancia ocasiona una regulación positiva compensadora de las funciones de los receptores NMDA. Se cree que esos cambios contribuyen con la aparición de tolerancia y dependencia del etanol, de los síntomas físicos y de algunos de los componentes afectivos y motivacionales de la abstinencia de alcohol. Por consiguiente, los mecanismos mediados por los receptores NMDA serían importantes con relación al alcoholismo. Asimismo, estos receptores pueden ser blancos útiles de acción de nuevas drogas para el tratamiento de los pacientes alcohólicos. Actualmente se investigan antagonistas no competitivos de los receptores NMDA como los compuestos que actúan en el canal del poro, en el sitio B de unión a la glicina o en la subunidad NR2B. El propósito de la presente revisión es resumir los resultados experimentales recientemente obtenidos mediante la utilización de nuevos antagonistas de los receptores NMDA.

Palabras clave
alcoholismo, dependencia del alcohol, abstinencia, receptor del NMDA, antagonista


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Abstract
Long-term alcohol exposure results in development of alcohol dependence as a consequence of changes in specific neurotransmitter functions. Accumulating evidence suggests that the N-methyl-d-aspartate (NMDA) type of ionotropic glutamate receptors is a particularly important site of ethanol's action. Ethanol potently inhibits NMDA receptors (NMDARs) and prolonged ethanol exposure produces a compensatory 'up-regulation' of the NMDAR functions. These changes are thought to contribute to the development of ethanol tolerance and dependence as well as both the physical symptoms and some of the affective and motivational components of alcohol withdrawal. Accordingly, NMDAR-mediated mechanisms may be important in alcoholism and NMDARs can be useful targets for novel anti-alcoholism drugs. Currently, several uncompetitive NMDAR antagonists like compounds acting in the channel pore, at the glycineB site or at the NR2B subunit of the NMDARs are under investigation. The aim of this review is to summarize the recent experimental results obtained with novel NMDAR antagonists.

Key words
alcoholism, alcohol dependence, withdrawal, NMDA receptor, antagonist


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Especialidades
Principal: Toxicología
Relacionadas: Bioquímica, Farmacología, Medicina Farmacéutica, Medicina Interna



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József Nagy, Laboratory for Molecular and Cellular Biology, Gedeon Richter Plc. Pharmacological and Drug Safety Research, H-1475, P.O.Box 27, Budapest, Hungría
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