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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/15995
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| Title: | Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia |
| Authors: | Huang, YH;Lin, SY;Ou, LC;Huang, WC;Chao, PK;Chang, YC;Chang, HF;Lee, PT;Yeh, TK;Kuo, YH;Tien, YW;Xi, JH;Tao, PL;Chen, PY;Chuang, JY;Shih, C;Chen, CT;Tung, CW;Loh, HH;Ueng, SH;Yeh, SH |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research;Center for Neuropsychiatric Research;NHRI Graduate Student Program |
| Abstract: | Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation. |
| Date: | 2024-07-17 |
| Relation: | Cell Chemical Biology. 2024 Jul 17;Article in Press. |
| Link to: | http://dx.doi.org/10.1016/j.chembiol.2024.06.013 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2451-9448&DestApp=IC2JCR |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85200421803 |
| Appears in Collections: | [葉修華] 期刊論文
[翁紹華] 期刊論文
[童俊維] 期刊論文
[陳炯東] 期刊論文
[石全(2014-2017)] 期刊論文
[葉燈光] 期刊論文
[陶寶綠] 期刊論文
[其他] 期刊論文
[林書玉] 期刊論文
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