A dual nociceptin and mu opioid receptor agonist exhibited robust antinociceptive effect with decreased side effects

被引：2

作者：

Hsu, Ying-Ting ^{[1
,3
,4
]}

Chen, Shen-Ren ^{[1
]}

Chang, Yung-Chiao ^{[1
]}

Chang, Hsiao-Fu ^{[1
]}

Yeh, Teng-Kuang ^{[1
]}

Chuang, Jian-Ying ^{[3
,4
]}

Loh, Horace H. ^{[5
,6
]}

Hsieh, Hsing-Pang ^{[1
]}

Ueng, Shau-Hua ^{[1
,2
]}

Yeh, Shiu-Hwa ^{[1
,3
,4
]}

机构：

[1] Natl Hlth Res Inst, Inst Biotechnol & Pharmaceut Res, Miaoli Cty 35053, Taiwan

[2] Natl Cheng Kung Univ, Coll Med, Sch Pharm, Tainan 701, Taiwan

[3] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Med Neurosci, Taipei 110, Taiwan

[4] Natl Hlth Res Inst, Taipei 110, Taiwan

[5] Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou 100005, Peoples R China

[6] Univ Minnesota, Med Sch, Dept Pharmacol, Minneapolis, MN 55455 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2023年 / 258卷

关键词：

Mu-opioid receptor; Antinociception; Addiction; Constipation; Antinociceptive tolerance; Reward effect;

D O I：

10.1016/j.ejmech.2023.115608

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The compelling demand of a consummate analgesic medication without addiction is rising due to the clinical mistreatment. Additionally, the series of severe untoward effects usually deterred the utilization while coping with serious pain. As a possible turning point, we revealed that compound 14 is a dual agonist of mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor in this study. More importantly, compound 14 achieves pain relieving at very small doses, meanwhile, reduces several unwanted side effects such as constipation, reward, tolerance and withdrawal effects. Here, we evaluated the antinociception and side ef-fects of this novel compound from wild type and humanized mice to further develop a safer prescription anal-gesic drug.

引用

页数：13

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