Los receptores muscarínicos como potencial objetivo terapéutico en la esquizofrenia
Resumen
La esquizofrenia es una enfermedad mental crónica caracterizada por tres conjuntos de síntomas: positivos, negativos y cognitivos. Aunque los primeros han logrado abordarse con los actuales fármacos antipsicóticos, un 20-30 % de pacientes no muestra respuesta y el perfil de efectos secundarios metabólicos y motores limita su uso en algunos casos. Durante mucho tiempo se explicó la presencia de dichas manifestaciones clínicas con la hipótesis dopaminérgica; sin embargo, terminó demostrándose como una explicación incompleta, a la vez que se involucraron otros sistemas de neurotransmisores, como el colinérgico. En este sentido, la acetilcolina se ha involucrado en funciones como la memoria, la atención y el aprendizaje, así como la regulación del sistema dopaminérgico. Además de los efectos antipsicóticos de fármacos que apuntan a sus receptores muscarínicos, como la xanomelina y la emraclidina, ha incrementado el interés en ese neurotransmisor como un objetivo en la búsqueda de nuevos medicamentos antipsicóticos. Así, el objetivo de este artículo es presentar una revisión de la literatura médica relacionada con la implicación de la acetilcolina, y particularmente de los receptores muscarínicos, en la esquizofrenia, y los esfuerzos por el desarrollo de nuevos fármacos antipsicóticos que apunten directamente al sistema colinérgico.
Abstract
Schizophrenia is a chronic mental illness characterized by three sets of symptoms: positive, negative, and cognitive. Although the positive symptoms have been managed with present-day antipsychotic agents, 20 to 30% of patients do not show response and the profile of metabolic and motor adverse effects limits its use in some cases. Furthermore, for a long time the existence of these clinical manifestations has been explained with the dopaminergic hypothesis. Nevertheless, it ended up being demonstrated as an incomplete explanation and other neurotransmitter systems have been involved, such as the cholinergic system. Acetylcholine has been related to mental functions such as memory, attention, and learning, just as with the regulation of the dopaminergic system. The above, together with the observed antipsychotic effects of drugs that target muscarinic receptors, such as xanomeline and emraclidine, have increased interest in this neurotransmitter as an objective in the search for new antipsychotic medications. This article aims to review the medical literature related to the involvement of acetylcholine, and particularly muscarinic receptors, in schizophrenia and the efforts to develop new antipsychotic drugs that directly target the cholinergic system.
Keywords: schizophrenia, acetylcholine, muscarinic receptors, cholinergic system, antipsychotic agents.
Palabras clave
Referencias
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DOI: https://doi.org/10.25009/eb.v15i38.2633
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