新型甲状腺素类似物在系统性和非侵入性施用时的神经变活性
Vladislav Deigin1, Nikolay Korobov2, Olga Volpina1
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St., 16/10, 117997 Moscow, Russia.
International journal of molecular sciences
|September 13, 2025
概括
新的甲状腺类药物显示出强大的止痛作用,D2在鼻内注射后显示出显著的疼痛缓解. 循环类似物 (D3,D4) 在口腔疼痛管理方面表现有前途,提供潜在的非侵入性药物应用.
科学领域:
- 药理学和神经科学 药理学和神经科学
- 药用化学 医学化学
背景情况:
- 神经调节疼痛和行为;dermorphin是一种来自Phyllomedusa sauvagei的强效神经,具有独特的D-Ala残留物.
- 德尔摩芬的结构激发了制药用途的类似物,特别是作为止痛药的开发.
研究的目的:
- 合成新的线性和循环性皮肤色素类似物.
- 为了评估这些类型的潜在的非侵入性止痛特性和制药应用.
主要方法:
- 线性德尔摩芬和2,5-狄基托皮佩拉 (2,5-DKP) 环皮多米米特的合成.
- 使用几内亚猪皮质 (GPI) 试验进行体外阿片类药物活性评估.
- 在体内通过热板和尾部试验评估镇痛功效.
- 使用开放场测试评估的行为影响.
主要成果:
- 皮肤氨基酸模拟物D2在体外表现出最高的阿片类活性;环酸D3和D4也表现出显著的活性.
- 在水尾试验中,D2在老鼠的鼻腔内注射产生了剂量依赖的止痛作用.
- 内注射D2显示了50%以上的止痛效果.
- 在大鼠中,D2抑制了行为反应.
- 循环类似物D3和D4在口服中显示出有前途的表现.
结论:
- 德尔摩芬类型D2,D3和D4是具有高阿片类活性的μ-阿片类受体的强烈激动剂.
- D2通过鼻内和腹腔内途径表现出显著的止痛作用.
- 循环性德尔摩芬类似物为口服止痛药开发提供了潜在的潜力.
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