@misc{10481/75477,
year = {2022},
month = {2},
url = {http://hdl.handle.net/10481/75477},
abstract = {The development of σ1 receptor antagonists hybridized with a H2S-donor is here reported. We aimed to obtain improved analgesic effects when compared to σ1 receptor antagonists or H2S-donors alone. In an in vivo model of sensory hypersensitivity, thioamide 1a induced analgesia which was synergistically enhanced when associated with the σ1 receptor antagonist BD-1063. The selective σ1 receptor agonist PRE-084 completely reversed this effect. Four thioamide H2S-σ1 receptor hybrids (5a8a) and their amide derivatives (5b8b) were synthesized. Compound 7a (AD164) robustly released H2S and showed selectivity for σ1 receptor over σ2 and opioid receptors. This compound induced marked analgesia that was reversed by PRE-084. The amide analogue 7b (AD163) showed only minimal analgesia. Further studies showed that 7a exhibited negligible acute toxicity, together with a favorable pharmacokinetic profile. To the best of our knowledge, compound 7a is the first dual-acting ligand with simultaneous H2S-release and σ1 antagonistic activities.},
organization = {This work was financially supported by University of Catania, PIA.CE.RI. 20202022 Linea di intervento 3 Starting Grant project CARETO (grant 57722172136). This study was partially supported by the Spanish State Research Agency (10.13039/501100011033) under the auspices of MINECO (grant number PID2019-108691RB-I00), the Andalusian Regional Government (grant CTS109), the University of Catania PIA.CE.RI. 20202022 Linea di intervento 2 project DETTAGLI (grant 57722172125), and by Italian MUR, PRIN 2017, Code: 201744BN5T.},
title = {Dual sigma-1 receptor antagonists and hydrogen sulfide-releasing compounds for pain treatment:  design, synthesis and pharmacological evaluation},
doi = {10.1016/j.ejmech.2021.114091},
author = {Dichiara, Maria and Artacho Cordón, Antonia and Turnaturi, Rita and Santos Caballero, Miriam and González Cano, Rafael and Pasquinucci, Lorella and Barbaraci, Carla and Rodríguez Gómez, Isabel María and Gómez Guzmán, Manuel and Marrazzo, Agostino and Cobos del Moral, Enrique José and Amata, Emanuele},
}