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阿替利珠单抗:作用机制、临床与转化科学。

Atogepant: Mechanism of action, clinical and translational science.

机构信息

Clinical Pharmacology, AbbVie, North Chicago, Illinois, USA.

Clinical Development, AbbVie, North Chicago, Illinois, USA.

出版信息

Clin Transl Sci. 2024 Jan;17(1):e13707. doi: 10.1111/cts.13707.


DOI:10.1111/cts.13707
PMID:38266063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10777605/
Abstract

Since the discovery of calcitonin gene-related peptide (CGRP) in 1982, its integral role in migraine pathophysiology, specifically migraine pain, has been demonstrated through cumulative scientific discoveries that have led to the development and approval of migraine-specific therapeutics. Today, eight drugs, including monoclonal antibodies and small molecule CGRP receptor antagonists, known as gepants, have received approval for acute or preventive treatment of migraine. The primary mechanism of these drugs is to block CGRP signaling, thus preventing CGRP-mediated nociception and neurogenic inflammation. Here, we focus on atogepant, a highly potent and selective gepant and the first and only oral medication approved for the preventive treatment of both episodic and chronic migraine in adults. In this article, we summarize the role of CGRP in migraine pathophysiology and the mechanism of action of atogepant. In addition, we provide an overview of atogepant's pharmacology and the key clinical trials and outcomes that have demonstrated the safety and efficacy of atogepant.

摘要

自 1982 年降钙素基因相关肽 (CGRP) 被发现以来,通过一系列科学发现,其在偏头痛发病机制中的整体作用,特别是偏头痛疼痛,已经得到了证实,这些发现导致了偏头痛特异性治疗药物的开发和批准。如今,已有八种药物(包括单克隆抗体和小分子 CGRP 受体拮抗剂,即 gepants)被批准用于偏头痛的急性或预防性治疗。这些药物的主要机制是阻断 CGRP 信号传导,从而防止 CGRP 介导的伤害感受和神经源性炎症。在这里,我们重点介绍 atogepant,一种高活性和选择性的 gepant,也是第一种也是唯一一种被批准用于成人预防治疗阵发性和慢性偏头痛的口服药物。在本文中,我们总结了 CGRP 在偏头痛发病机制中的作用和 atogepant 的作用机制。此外,我们还概述了 atogepant 的药理学以及已证明其安全性和疗效的关键临床试验和结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e1a/10777605/b9f47a2f9679/CTS-17-e13707-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e1a/10777605/b9f47a2f9679/CTS-17-e13707-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e1a/10777605/b9f47a2f9679/CTS-17-e13707-g001.jpg

相似文献

[1]
Atogepant: Mechanism of action, clinical and translational science.

Clin Transl Sci. 2024-1

[2]
Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex.

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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Lancet Neurol. 2024-4

[10]
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引用本文的文献

[1]
Identification of Neutrophil Extracellular Trap-Related Biomarkers in Diabetic Foot Ulcers Based on Bioinformatics.

J Inflamm Res. 2025-8-18

[2]
Small-molecule CGRP antagonist atogepant does not affect cortical spreading depression susceptibility in rats.

J Headache Pain. 2025-8-5

[3]
Gepants: Key Features of A Potent Therapeutic Option and Considerations in The Latin American Context.

Rev Neurol. 2025-6-25

[4]
Adverse events associated with gepants: a pharmacovigilance analysis based on the FDA adverse event reporting system.

J Headache Pain. 2025-6-23

[5]
Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines.

Signal Transduct Target Ther. 2025-3-5

[6]
Clinical Pharmacokinetics of Atogepant in Healthy Japanese and White Adults.

Neurol Ther. 2025-2

[7]
Combining treatments for migraine prophylaxis: the state-of-the-art.

J Headache Pain. 2024-12-5

本文引用的文献

[1]
Effects of CYP3A4 inhibition/induction and OATP inhibition on the pharmacokinetics of atogepant in healthy adults.

Pain Manag. 2023-8-31

[2]
Migraine Treatment: Towards New Pharmacological Targets.

Int J Mol Sci. 2023-7-31

[3]
Second messenger signalling bypasses CGRP receptor blockade to provoke migraine attacks in humans.

Brain. 2023-12-1

[4]
Ten open questions in migraine prophylaxis with monoclonal antibodies blocking the calcitonin-gene related peptide pathway: a narrative review.

J Headache Pain. 2023-8-1

[5]
Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet. 2023-9-2

[6]
New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy.

Cephalalgia. 2023-2

[7]
Once-daily oral atogepant for the long-term preventive treatment of migraine: Findings from a multicenter, randomized, open-label, phase 3 trial.

Headache. 2023-1

[8]
Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial.

Neurology. 2023-2-21

[9]
Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine.

Cephalalgia. 2022-11

[10]
Neurobiology of migraine progression.

Neurobiol Pain. 2022-6-9

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