Clinical benefits of a new piperidine-class AChE inhibitor

Alzheimer's disease (AD) is associated with a deficiency of acetylcholine ( ACh) in the forebrain that correlates with brain pathology and cognitive dy sfunction. The most promising approach to enhancing central ACh neurotransm ission has been the utilization of agents that inhibit cholinesterases whic h block its catabolism. Initially, the success of this strategy was limited by subtherapeutic levels of acetylcholinesterase (AChE) inhibition, tolera bility problems and toxicity of the first agents. Donepezil HCl represents a new chemical class of AChE inhibitors, the piperidines. In clinical trial s, donepezil has been shown to improve significantly cognition and global f unction 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 opt ion for AD patients. (C) 1999 Elsevier Science B.V./ECNP. All rights reserv ed.