Carbamate as a potential anti-Alzheimer's pharmacophore: A review

Alzheimer's disease (AD) is a progressive age-related neurodegenerative brain disorder, which leads to loss of memory and other cognitive dysfunction. The underlying mechanisms of AD pathogenesis are very complex and still not fully explored. Cholinergic neuronal loss, accumulation of amyloid plaque, metal ions dyshomeostasis, tau hyperphosphorylation, oxidative stress, neuroinflammation, and mitochondrial dysfunction are major hallmarks of AD. The current treatment options for AD are acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and NMDA receptor antagonists (memantine). These FDA-approved drugs mainly provide symptomatic relief without addressing the pathological aspects of disease progression. So, there is an urgent need for novel drug development that not only addresses the basic mechanisms of the disease but also shows the neuroprotective property. Various research groups across the globe are working on the development of multifunctional agents for AD amelioration using different core scaffolds for their design, and carbamate is among them. Rivastigmine was the first carbamate drug investigated for AD management. The carbamate fragment, a core scaffold of rivastigmine, act as a potential inhibitor of acetylcholinesterase. In this review, we summarize the last 10 years of research conducted on the modification of carbamate with different substituents which primarily target ChE inhibition, reduce oxidative stress, and modulate A ss aggregation.