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诱导cGMP介导的偏头痛发作是独立于CGRP受体激活的
Bianca Raffaelli1,2,3, Thien Phu Do1,4, Håkan Ashina1,5
1Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Cephalalgia : an international journal of headache
|June 8, 2024
概括
作为cGMP通路激活剂的西尔德纳菲尔,即使素基因相关 (CGRP) 通路被埃伦巴阻断,也会诱导偏头痛发作. 这表明cGMP通路的激活足以诱导偏头痛.
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.
背景情况:
- 周期性腺单酸盐 (cAMP) 和周期性关单酸盐 (cGMP) 途径在偏头痛发作中的作用已知,但它们的相互作用尚未完全理解.
- 素基因相关 (CGRP) 激活cAMP通路并触发偏头痛发作.
- 作为固酶-5抑制剂的西尔德纳菲尔激活了cGMP通路,可以诱导偏头痛发作.
研究的目的:
- 为了调查西尔德纳菲尔是否可以触发偏头痛发作,在偏头痛患者中,他们已经先前接受了CGRP受体抗体埃伦乌马布的治疗.
- 在偏头痛病理生理学中探索cGMP和CGRP/cAMP通路之间的相互作用.
主要方法:
- 一项随机,双盲,安慰剂控制的交叉研究与没有光环的偏头痛的成年人进行.
- 参与者接受了单次皮下注射埃伦乌马布 (140毫克),随后在两个不同的场合随机给予西尔德纳菲尔 (100毫克) 或安慰剂.
- 主要终点是服用后12小时内偏头痛发作的发生率,比较锡尔迪纳菲尔与安慰剂.
主要成果:
- 在16名参与者中,有10人 (63%) 在服用西尔德纳菲尔后经历了偏头痛发作,而在服用安慰剂后有3人 (19%) (p=0.016).
- 服用西尔代纳菲尔后,头痛强度和平均动脉血压显著增加,而心率显著增加.
- 西尔德纳菲尔在第一个小时内引起了平均动脉血压的显著下降和心率的同时增加.
结论:
- 偏头痛可以通过cGMP途径诱导,即使CGRP受体被阻止.
- 这些发现突显了cGMP途径在偏头痛发病过程中的独立作用.
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