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http://ir.nhri.org.tw/handle/3990099045/16241
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| Title: | DBPR116, a prodrug of BPRMU191, in combination with naltrexone as a safer opioid analgesic than morphine via peripheral administration |
| Authors: | Lin, SY;Chang, YC;Tien, YW;Kuo, YH;Chang, HF;Ou, LC;Chen, YP;Chang, KH;Hsu, YT;Huang, YC;Yang, CM;Law, PY;Xi, JH;Tao, PL;Loh, HH;Yeh, TK;Zhuang, H;Hsieh, HP;Shih, C;Chen, CT;Yeh, SH;Ueng, SH |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research;Center for Neuropsychiatric Research |
| Abstract: | The development of opioid analgesics with reduced adverse effects is an unmet need. In a previous study, we discovered a unique combination of BPRMU191 and morphinan antagonists that produced potent antinociception with reduced adverse effects after central administration (intrathecal or intracerebroventricular). BPRMU191/naltrexone exhibits notable in vitro and in vivo pharmacological properties. However, the poor blood-brain barrier penetrative ability of BPRMU191 restricts its clinical application. In this study, we utilized a prodrug strategy to deliver sufficient brain concentrations of BPRMU191 and selected compound 2 (DBPR116) with the best physicochemical and pharmacological properties among other in vivo active prodrugs. The in vivo pharmacological studies of compound 2/naltrexone, including thermally stimulated pain, cancer pain, constipation, sedation, psychological dependence, heart rate, and respiratory frequency measurements, demonstrated that it was a safer opioid analgesic than morphine in pain control. |
| Date: | 2024-10-29 |
| Relation: | Journal of Medicinal Chemistry. 2024 Oct 29;Article in Press. |
| Link to: | http://dx.doi.org/10.1021/acs.jmedchem.4c02107 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR |
| Appears in Collections: | [葉修華] 期刊論文
[翁紹華] 期刊論文
[林書玉] 期刊論文
[葉燈光] 期刊論文
[莊宏] 期刊論文
[謝興邦] 期刊論文
[石全(2014-2017)] 期刊論文
[陳炯東] 期刊論文
[陶寶綠] 期刊論文
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| PUB39473174.pdf | | 8093Kb | Adobe PDF | 12 | View/Open |
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