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Molecules ; 26(5)2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33668340

RESUMEN

Sigma-1 (σ-1) receptor agonists are considered as potential treatment for stroke. TS-157 is an alkoxyisoxazole-based σ-1 receptor agonist previously discovered in our group. The present study describes TS-157 profile in a battery of tests for cerebral ischemia. Initial evaluation demonstrated the compound's safety profile and blood-brain barrier permeability, as well as its ability to induce neurite outgrowth in vitro. The neurite outgrowth was shown to be mediated via σ-1 receptor agonism and involves upregulation of ERK phosphorylation (pERK). In particular, TS-157 also significantly accelerated the recovery of motor function in rats with transient middle cerebral artery occlusion (tMCAO). Overall, the results herein support the notion that σ-1 receptor agonists are potential therapeutics for stroke and further animal efficacy studies are warranted.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Actividad Motora/efectos de los fármacos , Proyección Neuronal/efectos de los fármacos , Oxazoles/farmacología , Receptores sigma/agonistas , Recuperación de la Función/efectos de los fármacos , Animales , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Estructura Molecular , Oxazoles/síntesis química , Oxazoles/química , Fosforilación/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptor Sigma-1
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