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Mecanismos de acción de los medicamentos antipsicóticos de segunda generación en la esquizofrenia: conocimientos obtenidos a partir de los estudios de imágenes cerebrales
Published online by Cambridge University Press: 12 May 2020
Resumen
Múltiples líneas de datos, incluidos estudios de imágenes recientes, indican que la esquizofrenia se asocia con un desequilibrio del sistema dopaminérgico que implica la hiperestimulación de los receptores D2 de dopamina (DA) estriatales y la infraestimulación de los receptores D1 de DA corticales. Presumiblemente, este endofenotipo de la DA surge del trasfondo de una disconectividad sináptica más general, que implica alteraciones en las funciones del IV-metil-D-aspartato (NMDA) y glutamatérgica (GLU). Igualmente importante es el hecho de que esta disregulación de la DA podría deteriorar más la transmisión del NMDA. Los medicamentos antipsicóticos de primera generación (APG) se caracterizan por elevada afinidad con los receptores D2 y, por lo general, su alta ocupación. La eficacia de los APG está limitada por una elevada incidencia de efectos secundarios extrapiramidades (ESEP). Los medicamentos antipsicóticos de segunda generación (ASG) muestran una reducción de la tendencia a los ESEP y un aumento modesto pero clínicamente significativo de la eficacia terapéutica. Comparado con los APG, la mejora de la acción terapéutica de los ASG deriva probablemente de un bloqueo más moderado del receptor D2. Revisaremos los efectos de los ASG sobre otros sistemas neurotransmisores y concluiremos haciendo resaltar la importancia de las estrategias terapéuticas dirigidas a aumentar directamente la transmisión del receptor D1 de DA prefrontal o la transmisión del NMDA para aumentar el efecto terapéutico del antagonismo moderado del receptor D2.
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- Copyright © European Psychiatric Association 2005
Footnotes
Abi-Dargham A, Laruelle M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia; insights from brain imaging studies. Eur Psychiatry 2005;20:15-27.
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