E-52862, also known as sigma-1 receptor antagonist (S1A, S1RA), as well as MR-309, is a
selectivesigma-1 receptorantagonist, with a reported
binding affinity of Ki = 17.0 ± 7.0 nM, selective over the
sigma-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 relieving
neuropathic pain and
pain in other sensitizing conditions, associated with an improvement of the emotional negative state.[2][3][4][5]
S1RA is being developed by
Esteve for the treatment of
neuropathic 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 selective
sigma-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.