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Author Topic: Neues langfristig wirkendes Schmerzmittel bei Mäusen erfolgreich  (Read 141 times)


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Ein neues Schmerzmittel als Ersatz für Opiode ist DER Wunschtraum. Der neue Stoff hat es immerhin schon bis zu den Mäusen gebracht.

Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice

James J. Sahn†, Galo L. Mejia‡, Pradipta R. Ray‡, Stephen F. Martin*† , and Theodore J. Price*‡
† Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States
‡ School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, Texas 75080, United States
ACS Chem. Neurosci., 2017, 8 (8), pp 1801–1811
DOI: 10.1021/acschemneuro.7b00200
Publication Date (Web): June 23, 2017
Copyright © 2017 American Chemical Society
*Mailing address: University of Texas at Austin, Welch Hall 5.224, 105 E 24th St., Stop A5300, Austin, TX 78712. Telephone: 512-471-3915. E-mail:, *Mailing address: School of Behavioral and Brain Sciences, University of Texas at Dallas, JO 4.212, 800 W. Campbell Rd., Richardson, TX 75080. Telephone: 972-883-4311. E-mail:
Abstract Image

Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is known to be a potential target for neuropathic pain therapeutics, and antagonists for this receptor are effective in preclinical models and are currently in phase II clinical trials. Conversely, relatively little is known about σ2R, which has recently been identified as transmembrane protein 97 (Tmem97). We generated a series of σ1R and σ2R/Tmem97 agonists and antagonists and tested them for efficacy in the mouse spared nerve injury (SNI) model. In agreement with previous reports, we find that σ1R ligands given intrathecally (IT) produce relief of SNI-induced mechanical hypersensitivity. We also find that the putative σ2R/Tmem97 agonists DKR-1005, DKR-1051, and UKH-1114 (Ki ∼ 46 nM) lead to relief of SNI-induced mechanical hypersensitivity, peaking at 48 h after dosing when given IT. This effect is blocked by the putative σ2R/Tmem97 antagonist SAS-0132. Systemic administration of UKH-1114 (10 mg/kg) relieves SNI-induced mechanical hypersensitivity for 48 h with a peak magnitude of effect equivalent to 100 mg/kg gabapentin and without producing any motor impairment. Finally, we find that the TMEM97 gene is expressed in mouse and human dorsal root ganglion (DRG) including populations of neurons that are involved in pain; however, the gene is also likely expressed in non-neuronal cells that may contribute to the observed behavioral effects. Our results show robust antineuropathic pain effects of σ1R and σ2R/Tmem97 ligands, demonstrate that σ2R/Tmem97 is a novel neuropathic pain target, and identify UKH-1114 as a lead molecule for further development.
Keywords: dorsal root ganglion; drug discovery; Neuropathic pain; sigma 1 receptor; sigma 2 receptor; Tmem97


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