一种新型TRPM8抗剂的皮下注射可以逆转过敏性感冒,同时减轻核心体温下降的影响
Michael S Gold1, Jorge B Pineda-Farias1, David Close2
1Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
British journal of pharmacology
|May 25, 2024
概括
这项研究表明,TRPM8抗剂VBJ103有效地治疗小鼠的寒冷过敏症. 虽然它会影响核心体温,但它的治疗潜力在疼痛管理方面仍然很有希望.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 疼痛研究 疼痛研究
背景情况:
- 暂时受体潜在的 Melastatin 8 (TRPM8) 通道与感冒和疼痛有关.
- 开发选择性TRPM8抗剂是治疗治疗疼痛的治疗目标.
- 以前的TRPM8抗剂面临挑战,包括影响核心体温 (CBT) 的副作用.
研究的目的:
- 描述TRPM8对手VBJ103,评估其选择性,有效性和对核心体温的影响.
- 评估VBJ103在化疗诱导的神经病痛的临床前模型中的治疗潜力.
- 调查VBJ103管理的安全概况和潜在责任.
主要方法:
- 对人类TRPA1和TRPV1通道进行选择性分析.
- 在体外安全性评估,包括多巴胺载体 (DAT) 抑制.
- 评估VBJ103在oxaliplatin诱导的寒冷过敏症小鼠模型中的疗效.
- 评估VBJ103对核心体温 (CBT) 的影响,通过皮下和腹腔内给药后的放射测量.
主要成果:
- VBJ103对TRPM8表现出选择性,在TRPA1和TRPV1没有对抗活性,尽管观察到低强度的TRPA1激活.
- 在接受过氧化治疗的小鼠中,VBJ103的皮下给药剂量依赖地减轻了感冒过敏.
- 系统性给予VBJ103,特别是在腹膜内,剂量取决于核心体温的下降.
- 多巴胺载体 (DAT) 的部分抑制是唯一发现的安全责任.
结论:
- VBJ103在临床前的寒冷过敏症模型中表现出治疗效果.
- 系统性给予VBJ103会影响核心体温,这是TRPM8向疗法的已知挑战.
- 进一步的研究是有必要的,以优化VBJ103的管理和缓解CBT相关的副作用临床翻译.
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