Rev. Soc. Esp. Dolor. 2021; 28(5): 292-297 / DOI: 10.20986/resed.2021.3891/2021
Borja Mugabure, Silvia González
RESUMEN
Los opioides son los fármacos más utilizados para el tratamiento del dolor agudo. Los opioides convencionales se utilizan ampliamente para el tratamiento del dolor agudo en el entorno postoperatorio. Sin embargo, una de las principales preocupaciones de dichos opioides es su ventana terapéutica, es decir, el intervalo entre las dosis que producen el efecto terapéutico deseado (analgesia) y las dosis que producen efectos adversos relacionados con los opioides (EARO) no deseados. Los opioides convencionales sobre receptores μ tienen una ventana terapéutica estrecha, en parte debido a su mecanismo de acción (MdA): se unen a los receptores μ y activan de forma no selectiva 2 vías de señalización intracelular, lo que provoca analgesia y EARO. Esta revisión explora el potencial clínico de los ligandos de los receptores μ con señalización diferencial. Los agentes con un MdA de "señalización diferencial" representan un enfoque innovador que puede mejorar la ventana terapéutica. Estos agentes modulan la actividad de los receptores μ para activar selectivamente las vías de señalización asociadas a la analgesia, al tiempo que limitan la actividad en las vías de señalización posteriores que conducen a los EARO. Por todo ello, la señalización diferencial puede satisfacer una necesidad no cubierta en el tratamiento del dolor postoperatorio. Oliceridina es un claro exponente de esta nueva generación.
ABSTRACT
Opioids are the most drugs used for the management of acute pain. Conventional opioids are widely used for acute pain management in the postoperative setting. However, a primary concern with conventional opioids is their therapeutic window, the range between doses that produce the desired therapeutic effect (analgesia) and doses that produce unwanted opioid-related adverse events (ORAEs). Conventional μ receptor opioids have a narrow therapeutic window in part because of their mechanism of action (MoA): they bind to μ receptors and non-selectively activate two intracellular signaling pathways, leading to analgesia and to ORAEs. This review explores the clinical potential of μ receptor ligands with differential signaling. Agents with a ’differential signaling” MoA represent an innovative approach that may enhance the therapeutic window. These agents modulate μ receptor activity to selectively engage downstream signaling pathways associated with analgesia while limiting activity in downstream signaling pathways that lead to ORAEs. Meanwhile, differential signaling may fulfill an unmet need in the management of postoperative pain. Oliceridine is a clear exponent of this new opioid generation.
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