Clinical benefits of a new piperidine-class AChE inhibitor

Abstract

Alzheimer's disease (AD) is associated with a deficiency of acetylcholine (ACh) in the forebrain that correlates with brain pathology and cognitive dysfunction. The most promising approach to enhancing central ACh neurotransmission has been the utilization of agents that inhibit cholinesterases which block its catabolism. Initially, the success of this strategy was limited by subtherapeutic levels of acetylcholinesterase (AChE) inhibition, tolerability problems and toxicity of the first agents. Donepezil HCI represents a new chemical class of AChE inhibitors, the piperidines. In clinical trials, donepezil has been shown to improve significantly cognition and global function in patients with mild to moderately severe AD, and has demonstrated an excellent tolerability and safety profile. These benefits, as well as a simple, once-daily dosing regimen, make donepezil a viable therapeutic option for AD patients.