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基于阿片肽-神经降压素的新型杂合肽，具有脊髓长效镇痛活性且倾向于延缓耐受性发展。

Novel opioid-neurotensin-based hybrid peptide with spinal long-lasting antinociceptive activity and a propensity to delay tolerance development.

作者信息

Frączek Karolina, Ferraiolo Mattia, Hermans Emmanuel, Bujalska-Zadrozny Magdalena, Kasarello Kaja, Erdei Anna, Kulik Kamila, Kowalczyk Agnieszka, Wojciechowski Piotr, Sulejczak Dorota, Sosnowski Piotr, Granica Sebastian, Benyhe Sandor, Kaczynska Katarzyna, Nagraba Lukasz, Stolarczyk Artur, Cudnoch-Jedrzejewska Agnieszka, Kleczkowska Patrycja

机构信息

Department of Pharmacodynamics, Centre for Preclinical Research (CBP), Medical University of Warsaw, Warsaw 02-097, Poland.

Laboratory of Neuropharmacology, Institute of Neurosciences, Université Catholique de Louvain, Brussels B-1200, Belgium.

出版信息

Acta Pharm Sin B. 2020 Aug;10(8):1440-1452. doi: 10.1016/j.apsb.2020.04.014. Epub 2020 May 1.

DOI:10.1016/j.apsb.2020.04.014
PMID:32963942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7488486/
Abstract

The behavioral responses exerted by spinal administration of the opioid-neurotensin hybrid peptide, PK23, were studied in adult male rats. The antinociceptive effect upon exposure to a thermal stimulus, as well as tolerance development, was assessed in an acute pain model. The PK23 chimera at a dose of 10 nmol/rat produced a potent pain-relieving effect, especially after its intrathecal administration. Compared with intrathecal morphine, this novel compound was found to possess a favourable side effect profile characterized by a reduced scratch reflex, delayed development of analgesic tolerance or an absence of motor impairments when given in the same manner, though some animals died following barrel rotation as a result of its i.c.v. administration (in particular at doses higher than 10 nmol/rat). Nonetheless, these results suggest the potential use of hybrid compounds encompassing both opioid and neurotensin structural fragments in pain management. This highlights the enormous potential of synthetic neurotensin analogues as promising future analgesics.

摘要

在成年雄性大鼠中研究了脊髓注射阿片-神经降压素杂合肽PK23所产生的行为反应。在急性疼痛模型中评估了暴露于热刺激时的抗伤害感受作用以及耐受性的发展。剂量为10 nmol/大鼠的PK23嵌合体产生了强大的止痛效果，尤其是在鞘内给药后。与鞘内注射吗啡相比，发现这种新型化合物具有良好的副作用特征，表现为抓挠反射减弱、镇痛耐受性发展延迟，或以相同方式给药时无运动障碍，尽管一些动物因脑室内给药（特别是剂量高于10 nmol/大鼠时）而在转桶试验后死亡。尽管如此，这些结果表明包含阿片和神经降压素结构片段的杂合化合物在疼痛管理中具有潜在用途。这突出了合成神经降压素类似物作为未来有前景的镇痛药的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/b2bed8f0e7cd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/03974c921ea5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/34e2d17af118/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/60d6f4dab114/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/3b1763c9a7f5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/f8e9cb4753ba/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/b6d0202a078a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/c4d93352f8e5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/b2bed8f0e7cd/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/03974c921ea5/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/34e2d17af118/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/60d6f4dab114/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/3b1763c9a7f5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/f8e9cb4753ba/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/b6d0202a078a/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/c4d93352f8e5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0de/7488486/b2bed8f0e7cd/gr7.jpg

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探讨偏头痛和神经病理性疼痛常见致病因素中的新型治疗靶点。
Int J Mol Sci. 2023 Feb 18;24(4):4114. doi: 10.3390/ijms24044114.
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