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.
Keywords: 1; 4-dihydropyridine; Alzheimer’s disease; Mtdls; calcium channel blockade; dihydropyrimidinone.