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

Paul J Bernard, Djamila Bellili, Lhassane Ismaili

Expert opinion on drug discovery 2024 Jan-Jun

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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. 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. 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.

Citation

Paul J Bernard, Djamila Bellili, Lhassane Ismaili. Calcium channel blockers' contribution to overcoming Current drug discovery challenges in Alzheimer's disease. Expert opinion on drug discovery. 2024 Jan-Jun;19(1):21-32