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针对偏头痛的靶向垂体腺苷酸环化酶激活肽疗法。

Targeted Pituitary Adenylate Cyclase-Activating Peptide Therapies for Migraine.

机构信息

Danish Headache Center and Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2600, Glostrup, Copenhagen, Denmark.

出版信息

Neurotherapeutics. 2018 Apr;15(2):371-376. doi: 10.1007/s13311-017-0596-x.

DOI:10.1007/s13311-017-0596-x
PMID:29464574
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5935633/
Abstract

Here, we review the role of pituitary adenylate cyclase-activating peptide-38 (PACAP38) in migraine pathophysiology and data implicating PAC receptor as a future drug target in migraine. Much remains to be fully elucidated about migraine pathophysiology, but recent attention has focused on signaling molecule PACAP38, a vasodilator able to induce migraine attacks in patients who experience migraine without aura. PACAP38, with marked and sustained effect, dilates extracerebral arteries but not the middle cerebral artery. The selective affinity of PACAP38 to the PAC receptor makes this receptor a highly interesting and potential novel target for migraine treatment. Efficacy of antagonism of this receptor should be investigated in randomized clinical trials.

摘要

在这里,我们回顾了垂体腺苷酸环化酶激活肽-38(PACAP38)在偏头痛发病机制中的作用,以及 PAC 受体作为偏头痛未来药物靶点的数据。偏头痛发病机制仍有许多尚未完全阐明,但最近的研究重点是信号分子 PACAP38,它是一种血管扩张剂,能够在没有先兆的偏头痛患者中引发偏头痛发作。PACAP38 具有显著而持久的作用,可扩张颅外动脉,但不扩张大脑中动脉。PACAP38 对 PAC 受体的选择性亲和力使该受体成为偏头痛治疗的一个非常有趣和有潜力的新靶点。应该在随机临床试验中研究拮抗该受体的疗效。

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本文引用的文献

1
Chronic changes in pituitary adenylate cyclase-activating polypeptide and related receptors in response to repeated chemical dural stimulation in rats.大鼠反复化学性硬脑膜刺激后垂体腺苷酸环化酶激活多肽及相关受体的慢性变化
Mol Pain. 2017 Jan-Dec;13:1744806917720361. doi: 10.1177/1744806917720361.
2
The Trigeminovascular Pathway: Role of CGRP and CGRP Receptors in Migraine.三叉血管通路:降钙素基因相关肽及其受体在偏头痛中的作用。
Headache. 2017 May;57 Suppl 2:47-55. doi: 10.1111/head.13081.
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Neuropeptides as a Marker for Chronic Headache.神经肽作为慢性头痛的一个标志物
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4
G Protein-Coupled Receptor Endosomal Signaling and Regulation of Neuronal Excitability and Stress Responses: Signaling Options and Lessons From the PAC1 Receptor.G蛋白偶联受体内体信号传导与神经元兴奋性及应激反应的调节:信号传导选项及PAC1受体的经验教训
J Cell Physiol. 2017 Apr;232(4):698-706. doi: 10.1002/jcp.25615. Epub 2016 Oct 12.
5
No Change in Interictal PACAP Levels in Peripheral Blood in Women With Chronic Migraine.慢性偏头痛女性外周血中无肽能神经肽 PACAP 水平变化。
Headache. 2016 Oct;56(9):1448-1454. doi: 10.1111/head.12949. Epub 2016 Sep 16.
6
PACAP38 dose-response pilot study in migraine patients.偏头痛患者中PACAP38剂量反应的初步研究。
Cephalalgia. 2017 Apr;37(4):391-395. doi: 10.1177/0333102416644435. Epub 2016 Apr 15.
7
Part I: Pituitary adenylate cyclase-activating polypeptide-38 induced migraine-like attacks in patients with and without familial aggregation of migraine.第一部分:垂体腺苷酸环化酶激活多肽-38在有或无偏头痛家族聚集性的患者中诱发偏头痛样发作。
Cephalalgia. 2017 Feb;37(2):125-135. doi: 10.1177/0333102416639516. Epub 2016 Jul 11.
8
Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial.AMG 334 预防阵发性偏头痛的安全性和有效性:一项随机、双盲、安慰剂对照、2 期临床试验。
Lancet Neurol. 2016 Apr;15(4):382-90. doi: 10.1016/S1474-4422(16)00019-3. Epub 2016 Feb 12.
9
Change in brain network connectivity during PACAP38-induced migraine attacks: A resting-state functional MRI study.在 PACAP38 诱导的偏头痛发作期间大脑网络连接的变化:一项静息态功能磁共振成像研究。
Neurology. 2016 Jan 12;86(2):180-7. doi: 10.1212/WNL.0000000000002261. Epub 2015 Dec 16.
10
Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine.神经元 PAC1 受体介导三叉颈神经元的延迟激活和敏化:与偏头痛的相关性。
Sci Transl Med. 2015 Oct 7;7(308):308ra157. doi: 10.1126/scitranslmed.aaa7557.