Calcium channel blockers' contribution to overcoming Current drug discovery challenges in Alzheimer's disease.

IF 6 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Drug Discovery Pub Date : 2024-01-01 Epub Date: 2024-01-08 DOI:10.1080/17460441.2023.2266994

Paul J Bernard, Djamila Bellili, Lhassane Ismaili

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引用次数: 0

Abstract

Introduction: Alzheimer's disease (AD) is a progressive, irreversible, and multifactorial brain disorder that gradually and insidiously destroys individual's memory, thinking, and other cognitive abilities.

Areas covered: In this perspective, the authors examine the complex and multifactorial nature of Alzheimer's disease and believe that the best approach to develop new drugs is the MTDL strategy, which obviously faces several challenges. These challenges include identifying the key combination of targets and their suitability for coordinated actions, as well as developing an acceptable pharmacokinetic and toxicological profile to deliver a drug candidate.

Expert opinion: Since calcium plays a crucial role in the pathology of AD, a polypharmacological approach with calcium channel blockers reinforced by activities targeting other factors involved in AD is a serious option in our opinion. This is exemplified by a phase III clinical trial using a drug combination approach with Losartan, Amlodipine (a calcium channel blocker), and Atorvastatin, as well as several MTDL-based calcium channel blockade approaches with a promising in vitro and in vivo profile.

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钙通道阻滞剂对克服当前阿尔茨海默病药物发现挑战的贡献。

引言：阿尔茨海默病（AD）是一种进行性、不可逆和多因素的大脑疾病，它会逐渐和暗中破坏个人的记忆、思维和其他认知能力。涵盖的领域：从这个角度来看，作者研究了阿尔茨海默病的复杂性和多因素性，并认为开发新药的最佳方法是MTDL策略，这显然面临着几个挑战。这些挑战包括确定靶标的关键组合及其协同作用的适用性，以及开发可接受的药代动力学和毒理学特征来提供候选药物。专家意见：由于钙在AD的病理学中起着至关重要的作用，我们认为，通过针对AD相关其他因素的活动来加强钙通道阻滞剂的多药治疗方法是一个重要的选择。一项III期临床试验证明了这一点，该试验使用了氯沙坦、氨氯地平（一种钙通道阻滞剂）和阿托伐他汀的药物组合方法，以及几种基于MTDL的钙通道阻断方法，具有良好的体外和体内特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Opinion on Drug Discovery 医学-药学

CiteScore

10.20

自引率

1.60%

发文量

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.