Neuropharmacology, volume 166, pages 107678

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

Po-Kuan Chao ¹

Hsiao-Wei Chang ¹

Wan-Ting Chang ¹

Teng-Kuang Yeh ¹

Li Ou ¹

Jian-Ying Chuang ²

John Tsu An Hsu ¹

Pao-Luh Tao ³

Horace H. Hoh ⁴

Chuan Shih ¹

Shau Hua Ueng ^{5, 6}

Shiu-Hwa Yeh ^{5, 7}

Hide authors affiliations Show authors affiliations: 7 affiliations

Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan |

The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, 110, Taiwan. |

Center for Neuropsychiatric Research, National Heath Research Institutes, Zhunan, Miaoli County, 35053, Taiwan |

⁴

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455-0217, USA |

⁵

Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, 35053, Taiwan |

⁶

School of Pharmacy, National Cheng Kung University, Tainan, Taiwan, ROC |

⁷

The PhD Program for Neural Regenerative Medicine, Taipei Medical University, Taipei, 110, Taiwan |

Publication type: Journal Article

Publication date: 2020-04-01

Elsevier

Journal: Neuropharmacology

Quartile SCImago

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Impact factor: 4.7

ISSN: 00283908, 18737064

DOI: 10.1016/j.neuropharm.2019.107678

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Pharmacology

Cellular and Molecular Neuroscience

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. This article is part of the Special Issue entitled ‘New Vistas in Opioid Pharmacology’.

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GOST |

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GOST Copy

Chao P. et al. BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine // Neuropharmacology. 2020. Vol. 166. p. 107678.

GOST all authors (up to 50) Copy

Chao P., Chang H., Chang W., Yeh T., Ou L., Chuang J., Tsu An Hsu J., Tao P., Hoh H. H., Shih C., Ueng S. H., Yeh S. BPR1M97, a dual mu opioid receptor/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine // Neuropharmacology. 2020. Vol. 166. p. 107678.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1016/j.neuropharm.2019.107678

UR - https://doi.org/10.1016/j.neuropharm.2019.107678

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

T2 - Neuropharmacology

AU - Chao, Po-Kuan

AU - Chang, Hsiao-Wei

AU - Chang, Wan-Ting

AU - Yeh, Teng-Kuang

AU - Ou, Li

AU - Chuang, Jian-Ying

AU - Tsu An Hsu, John

AU - Tao, Pao-Luh

AU - Hoh, Horace H.

AU - Shih, Chuan

AU - Ueng, Shau Hua

AU - Yeh, Shiu-Hwa

PY - 2020

DA - 2020/04/01 00:00:00

PB - Elsevier

SP - 107678

VL - 166

SN - 0028-3908

SN - 1873-7064

ER -

BibTex

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BibTex Copy

@article{2020_Chao,

author = {Po-Kuan Chao and Hsiao-Wei Chang and Wan-Ting Chang and Teng-Kuang Yeh and Li Ou and Jian-Ying Chuang and John Tsu An Hsu and Pao-Luh Tao and Horace H. Hoh and Chuan Shih and Shau Hua Ueng and Shiu-Hwa Yeh},

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

journal = {Neuropharmacology},

year = {2020},

volume = {166},

publisher = {Elsevier},

month = {apr},

url = {https://doi.org/10.1016/j.neuropharm.2019.107678},

pages = {107678},

doi = {10.1016/j.neuropharm.2019.107678}

}

Found error?

Publisher

Elsevier

Journal

Neuropharmacology

Quartile SCImago

Quartile WOS

Impact factor

4.7

ISSN

00283908 (Print)
18737064 (Electronic)