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用于偏头痛预防的 atogepant 的临床前发现和开发。

The preclinical discovery and development of atogepant for migraine prophylaxis.

机构信息

Azienda Unità Sanitaria Locale di Modena, Modena, Italy.

Department of Neurology, Odense University Hospital, Odense, Denmark.

出版信息

Expert Opin Drug Discov. 2024 Jul;19(7):783-788. doi: 10.1080/17460441.2024.2365379. Epub 2024 Jun 10.


DOI:10.1080/17460441.2024.2365379
PMID:38856039
Abstract

INTRODUCTION: Atogepant is a selective calcitonin gene-related peptide (CGRP) receptor antagonist that is utilized in adults for the prevention of episodic and chronic migraine. Cumulative findings support the involvement of CGRP in migraine pathophysiology, and atogepant functions by competitively antagonizing CGRP receptors, which results in the inhibition of trigeminovascular nociception. The mechanism of action addresses the cause of migraine pain, providing an effective preventive treatment option. AREAS COVERED: The key milestones in its development, including preclinical achievements, phase I, II, and III clinical trials, and regulatory approvals are reviewed. Additionally, clinical efficacy, safety profile, and tolerability of atogepant are discussed. The literature review is based on a comprehensive search of English peer-reviewed articles from various electronic databases, including PubMed and ClinicalTrials.gov. EXPERT OPINION: The development of atogepant represents a significant breakthrough in migraine prevention, particularly due to its improved safety profile that reduces the risk of liver injury, which was a major limitation of first-generation gepants. Drug-drug interaction studies with atogepant highlight the necessity for more inclusive study populations. Given that migraine disproportionately affects females, future clinical development programs should include diverse patient demographics to ensure the findings are generalizable to all individuals suffering from migraine.

摘要

简介:阿替利珠单抗是一种选择性降钙素基因相关肽(CGRP)受体拮抗剂,用于预防成人发作性和慢性偏头痛。累积的研究结果支持 CGRP 在偏头痛病理生理学中的作用,阿替利珠单抗通过竞争性拮抗 CGRP 受体起作用,从而抑制三叉神经血管伤害性感受器。其作用机制针对偏头痛疼痛的原因,提供了一种有效的预防治疗选择。

涵盖的领域:综述了其开发过程中的关键里程碑,包括临床前成就、I 期、II 期和 III 期临床试验以及监管批准。此外,还讨论了阿替利珠单抗的临床疗效、安全性和耐受性。文献综述基于对来自 PubMed 和 ClinicalTrials.gov 等各种电子数据库的英文同行评议文章的全面搜索。

专家意见:阿替利珠单抗的开发是偏头痛预防的重大突破,特别是由于其改善的安全性降低了肝损伤的风险,这是第一代 gepants 的主要局限性。阿替利珠单抗的药物相互作用研究强调了更全面的研究人群的必要性。鉴于偏头痛在女性中更为普遍,未来的临床开发计划应包括更多样化的患者人群,以确保研究结果适用于所有偏头痛患者。

相似文献

[1]
The preclinical discovery and development of atogepant for migraine prophylaxis.

Expert Opin Drug Discov. 2024-7

[2]
Atogepant: an emerging treatment for migraine.

Expert Opin Pharmacother. 2022-4

[3]
Gepants for the treatment of migraine.

Expert Opin Investig Drugs. 2019-5-17

[4]
Efficacy and safety of atogepant, a small molecule CGRP receptor antagonist, for the preventive treatment of migraine: a systematic review and meta-analysis.

J Headache Pain. 2024-7-19

[5]
CGRP monoclonal antibodies and CGRP receptor antagonists (Gepants) in migraine prevention.

Handb Clin Neurol. 2024

[6]
CGRP inhibitors for migraine prophylaxis: a safety review.

Expert Opin Drug Saf. 2020-10

[7]
Atogepant: First Approval.

Drugs. 2022-1

[8]
Calcitonin Gene-Related Peptide Modulators - The History and Renaissance of a New Migraine Drug Class.

Headache. 2019-4-25

[9]
History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment.

Headache. 2018-9-22

[10]
Emerging drugs for the preventive treatment of migraine: a review of CGRP monoclonal antibodies and gepants trials.

Expert Opin Emerg Drugs. 2023-12

引用本文的文献

[1]
"The efficacy and safety of Atogepant for migraine prophylaxis: a systematic review and meta-analysis of randomized controlled trials".

BMC Neurol. 2025-8-9

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

J Headache Pain. 2025-8-5

[3]
The Role of Trifluoromethyl and Trifluoromethoxy Groups in Medicinal Chemistry: Implications for Drug Design.

Molecules. 2025-7-18

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

J Headache Pain. 2025-6-23

[5]
Pharmacokinetics of Atogepant in Healthy Lactating Female Participants: Results from a Phase 1 Lactation Study.

Neurol Ther. 2025-6-2

[6]
Variant angina associated with a CGRP receptor antagonist: a case report.

BMC Neurol. 2025-5-29

[7]
Single-centre, randomised and double-blind clinical trial on the efficacy of transcutaneous auricular vagus nerve stimulation in preventing and treating primary headache in children and adolescents: a study protocol.

BMJ Open. 2025-3-12

[8]
Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine.

Drug Des Devel Ther. 2025-2-19

[9]
Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders.

Molecules. 2025-1-27

[10]
Role of memantine in adult migraine: a systematic review and network meta-analysis to compare memantine with existing migraine preventive medications.

Front Pharmacol. 2024-12-18

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