E-52862, also known assigma-1 receptor antagonist (S1A,S1RA), as well asMR-309, is aselectivesigma-1 receptorantagonist, with a reportedbinding affinity ofKi =17.0 ± 7.0 nM, selective over thesigma-2 receptor and against a panel of other 170 receptors, enzymes, transporters and ion channels.[1][2] In preclinical studies, S1RA has demonstrated efficacy in relievingneuropathic pain andpain in other sensitizing conditions, associated with an improvement of the emotional negative state.[2][3][4][5]
S1RA is being developed byEsteve for the treatment ofneuropathic pain and the potentiation of opioid analgesia and has successfully completed Phase I clinical trials showing good safety and tolerability, and a pharmacokinetic profile compatible with once a day oral administration.[6] Phase II clinical trials are currently underway, making S1RA the first selectivesigma-1 receptorantagonist evaluated in humans for these conditions.
^Díaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C, Serafini MT, Burgueño J, Zamanillo D, Merlos M, Vela JM, Almansa C (2012). "Synthesis and Biological Evaluation of the 1-Arylpyrazole Class of σ1 Receptor Antagonists: Identification of 4-{2-[5-Methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862)".J. Med. Chem.55 (19):8211–8224.doi:10.1021/jm3007323.PMID22784008.
^Bura AS, Guegan T, Zamanillo D, Vela JM, Maldonado R (2013). "Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain".Eur. J. Pain.17 (6):832–843.doi:10.1002/j.1532-2149.2012.00251.x.hdl:10230/23299.PMID23172791.
