New Trends in the Design of Drugs Against Alzheimer's Disease

Abstract

First described by Alois Alzheimer in 1907, Alzheimer's disease (AD) is the most common dementia type, affecting approximately 20 million people worldwide. As the population is getting older, AD is a growing health problem. AD is currently treated by symptomatic drugs, the acetylcholinesterase inhibitors, based on the cholinergic hypothesis (1976). During the past decade, advances in neurobiology have conducted to the identification of new targets. Although some of these innovative approaches tend to delay onset of AD, others are still symptomatic. In this review, we present an overview of the several strategies and new classes of compounds against AD.

Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2-ene linker and evaluation of their reactivation activity against tabun- and paraoxon-inhibited acetylcholinesterase

“…The presence of oxime is essential for all reactivators [2]. The position of oxime determines which type of OPC will be better accessible for reactivation [18 -19,33 -34].…”

“…The reactivators of AChE used are oximes e.g. pralidoxime, obidoxime, HI-6 ( Figure 2) [2,6]. Nevertheless, every type of OPC needs a specific structure of its AChE reactivator due to the huge variety of substituents on the central phosphorus atom in the molecule of the OPC [6].…”

“…Several potent substances against GA-inhibited AChE were investigated recently in our group -K048 (1) and K075 (2) (Figure 3) [20][21][22]. In order to combine these two molecules, new potential reactivators were designed.…”

Novel Anti-Alzheimer's Dimer Bis(7)-Cognitin: Cellular and Molecular Mechanisms of Neuroprotection Through Multiple Targets

“…Tacrine is rarely prescribed nowadays due to serious side effects, including hepatotoxicity. Galanthamine, rivastigmine, and donepezil are most effective when treatment is begun in the early stages of AD 6,15 but show the gastrointestinal side effects (peripheral cholinergic effects). The use of HA as a therapeutic for AD has been inhibited in the U.S., as well as other countries, because of problems of intellectual property protection (absence of a patent) and high cost (the natural resource is rare).…”

“…Furthermore, half of those who have taken these drugs showed no response. 6,15 Although memantine has been approved for treatment of moderate to severe AD, its clinical efficacy seems to be less than that of the AChE inhibitors. It is increasingly being used as an adjuvant to cholinesterase inhibitor therapy, and studies indicate that targeting both the cholinergic and glutamate pathway could result in better clinical outcomes.…”