用于偏头痛预防的阿托吉潘的临床前发现和开发。

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Drug Discovery Pub Date : 2024-07-01 Epub Date: 2024-06-10 DOI:10.1080/17460441.2024.2365379
Carlo Baraldi, Dagmar Beier, Paolo Martelletti, Lanfranco Pellesi
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引用次数: 0

摘要

简介阿托吉潘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。阿托格潘通过竞争性拮抗降钙素相关肽受体,从而抑制三叉神经血管的痛觉。其作用机制针对偏头痛的病因,提供了一种有效的预防性治疗方案:回顾了该药物研发过程中的重要里程碑,包括临床前研究成果、I、II 和 III 期临床试验以及监管部门的批准。此外,还讨论了阿托格潘的临床疗效、安全性和耐受性。文献综述基于对各种电子数据库(包括 PubMed 和 ClinicalTrials.gov)中英文同行评审文章的全面检索:阿托格潘的开发是偏头痛预防领域的重大突破,特别是由于其安全性得到了改善,降低了肝损伤的风险,而肝损伤是第一代格潘的主要局限。对阿托格潘进行的药物相互作用研究突出表明,研究对象必须更具包容性。鉴于偏头痛对女性的影响尤为严重,未来的临床开发项目应包括不同的患者人群,以确保研究结果可推广到所有偏头痛患者。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The preclinical discovery and development of atogepant for migraine prophylaxis.

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.

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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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