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偏头痛治疗的新兴靶点

Emerging Targets for Migraine Treatment.

作者信息

Moreno-Ajona David, Villar-Martínez María Dolores, Goadsby Peter James

机构信息

Basic and Clinical Neurosciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

NIHR-Wellcome Trust King's Clinical Research Facility/SLaM Biomedical Research Centre, King's College Hospital, London, United Kingdom; Department of Neurology, University of California, Los Angeles, Los Angeles CA USA.

出版信息

Neurol India. 2021 Mar-Apr;69(Supplement):S98-S104. doi: 10.4103/0028-3886.315989.

Abstract

BACKGROUND

While understanding the pathophysiology of migraine has led to CGRP-based treatments, other potential targets have also been implicated in migraine.

OBJECTIVES

To catalog new promising targets for the treatment of migraine.

METHODS

We completed a literature review focusing on 5HT, PACAP, melatonin, and orexins.

RESULTS

The 5HT receptor agonist lasmiditan, following two positive randomized placebo-controlled trials, was FDA-approved for the acute treatment of migraine. PACAP-38 has shown analogous evidence to what was obtained for CGRP with its localization in key structures, provocation tests, and positive studies when antagonizing its receptor in animal models, although a PAC-1 receptor monoclonal antibody study was negative. Melatonin has undergone several randomized controlled trials showing a positive trend. Filorexant is the only dual orexin receptor antagonist, which was tested in humans with negative results.

CONCLUSIONS

Further and ongoing studies will determine the utility of these new therapies with lasmiditan and melatonin having demonstrated efficacy for the treatment of migraine.

摘要

背景

虽然对偏头痛病理生理学的理解催生了基于降钙素基因相关肽(CGRP)的治疗方法,但其他潜在靶点也与偏头痛有关。

目的

梳理偏头痛治疗的新的有前景的靶点。

方法

我们完成了一项聚焦于5-羟色胺(5HT)、垂体腺苷酸环化酶激活肽(PACAP)、褪黑素和食欲素的文献综述。

结果

5HT受体激动剂拉米地坦在两项阳性随机安慰剂对照试验后,获得美国食品药品监督管理局(FDA)批准用于偏头痛的急性治疗。PACAP-38在关键结构中的定位、激发试验以及在动物模型中拮抗其受体时的阳性研究结果方面,显示出与CGRP类似的证据,尽管一项PAC-1受体单克隆抗体研究结果为阴性。褪黑素已进行了多项随机对照试验,显示出积极趋势。非雷司他是唯一一种在人体中进行测试但结果为阴性的双重食欲素受体拮抗剂。

结论

进一步的和正在进行的研究将确定这些新疗法的效用,其中拉米地坦和褪黑素已证明对偏头痛治疗有效。

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