BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine

Po Kuan Chao, Hsiao Fu Chang, Wan Ting Chang, Teng Kuang Yeh, Li Chin Ou, Jian Ying Chuang, John Tsu-An Hsu, Pao Luh Tao, Horace H. Loh, Chuan Shih, Shau Hua Ueng, Shiu Hwa Yeh

研究成果: 雜誌貢獻文章

摘要

There is unmet need to design an analgesic with fewer side effects for severe pain management. Although traditional opioids are the most effective painkillers, they are accompanied by severe adverse responses, such as respiratory depression, constipation symptoms, tolerance, withdrawal, and addiction. We indicated BPR1M97 as a dual mu opioid receptor (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor full agonist and investigated the pharmacology of BPR1M97 in multiple animal models. In vitro studies on BPR1M97 were assessed using cyclic-adenosine monophosphate production, β-arrestin, internalization, and membrane potential assays. In vivo studies were characterized using the tail-flick, tail-clip, lung functional, heart functional, acetone drop, von Frey hair, charcoal meal, glass bead, locomotor activity, conditioned place preference (CPP) and naloxone precipitation tests. BPR1M97 elicited full agonist properties for all cell-based assays tested in MOP-expressing cells. However, it acted as a G protein-biased agonist for NOP. BPR1M97 initiated faster antinociceptive effects at 10 min after subcutaneous injection and elicited better analgesia in cancer-induced pain than morphine. Unlike morphine, BPR1M97 caused less respiratory, cardiovascular, and gastrointestinal dysfunction. In addition, BPR1M97 decreased global activity and induced less withdrawal jumping precipitated by naloxone. Thus, BPR1M97 could serve as a novel small molecule dual receptor agonist for antinociception with fewer side effects than morphine.

原文英語
文章編號107678
期刊Neuropharmacology
DOIs
出版狀態已發佈 - 一月 1 2019

指紋

Peptide Receptors
mu Opioid Receptor
Morphine
Naloxone
Arrestin
Substance Withdrawal Syndrome
Charcoal
Subcutaneous Injections
Constipation
Pain Management
Locomotion
Acetone
GTP-Binding Proteins
Surgical Instruments
Respiratory Insufficiency
Cyclic AMP
Membrane Potentials
Analgesia
Opioid Analgesics
Glass

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

引用此文

BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine. / Chao, Po Kuan; Chang, Hsiao Fu; Chang, Wan Ting; Yeh, Teng Kuang; Ou, Li Chin; Chuang, Jian Ying; Tsu-An Hsu, John; Tao, Pao Luh; Loh, Horace H.; Shih, Chuan; Ueng, Shau Hua; Yeh, Shiu Hwa.

於: Neuropharmacology, 01.01.2019.

研究成果: 雜誌貢獻文章

Chao, Po Kuan ; Chang, Hsiao Fu ; Chang, Wan Ting ; Yeh, Teng Kuang ; Ou, Li Chin ; Chuang, Jian Ying ; Tsu-An Hsu, John ; Tao, Pao Luh ; Loh, Horace H. ; Shih, Chuan ; Ueng, Shau Hua ; Yeh, Shiu Hwa. / BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine. 於: Neuropharmacology. 2019.
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abstract = "There is unmet need to design an analgesic with fewer side effects for severe pain management. Although traditional opioids are the most effective painkillers, they are accompanied by severe adverse responses, such as respiratory depression, constipation symptoms, tolerance, withdrawal, and addiction. We indicated BPR1M97 as a dual mu opioid receptor (MOP)/nociceptin-orphanin FQ peptide (NOP) receptor full agonist and investigated the pharmacology of BPR1M97 in multiple animal models. In vitro studies on BPR1M97 were assessed using cyclic-adenosine monophosphate production, β-arrestin, internalization, and membrane potential assays. In vivo studies were characterized using the tail-flick, tail-clip, lung functional, heart functional, acetone drop, von Frey hair, charcoal meal, glass bead, locomotor activity, conditioned place preference (CPP) and naloxone precipitation tests. BPR1M97 elicited full agonist properties for all cell-based assays tested in MOP-expressing cells. However, it acted as a G protein-biased agonist for NOP. BPR1M97 initiated faster antinociceptive effects at 10 min after subcutaneous injection and elicited better analgesia in cancer-induced pain than morphine. Unlike morphine, BPR1M97 caused less respiratory, cardiovascular, and gastrointestinal dysfunction. In addition, BPR1M97 decreased global activity and induced less withdrawal jumping precipitated by naloxone. Thus, BPR1M97 could serve as a novel small molecule dual receptor agonist for antinociception with fewer side effects than morphine.",
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AU - Chang, Wan Ting

AU - Yeh, Teng Kuang

AU - Ou, Li Chin

AU - Chuang, Jian Ying

AU - Tsu-An Hsu, John

AU - Tao, Pao Luh

AU - Loh, Horace H.

AU - Shih, Chuan

AU - Ueng, Shau Hua

AU - Yeh, Shiu Hwa

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