Health & Environmental Research Online (HERO)


Print Feedback Export to File
8307833 
Journal Article 
Donepezil 
Asiri, YA; Mostafa, GAE 
2010 
Academic Press Inc. 
Profiles of Drug Substances, Excipients and Related Methodology 
35 
117-150 
English 
Donepezil hydrochloride is a white powder and is freely soluble in water and in chloroform, sparingly soluble in glacial acetic acid and in ethanol, slightly soluble in acetonitrile, very slightly soluble in ethyl acetate, and insoluble in n-hexane. Donepezil hydrochloride (E2020) is the second drug approved by the United States food and drug administration (FDA) for the treatment of mild to moderate alzheimer's diseases (AD). It is a new class of acetyl cholinesterase (AChE) inhibitor having an N-benzylpiperidine and an indanone moiety that shows longer and more selective action. Donepezil HCl, a piperidine, is a highly selective inhibitor of the enzyme AChE that is chemically unique from other AChE inhibitors. In vitro and preclinical studies have demonstrated that Donepezil is approximately 1200 times more selective for AChE in the brain than for butyrylcholinesterase (BuChE) in the periphery. Phase II and III studies conducted in the United States have shown that Donepezil produces statistically significant improvements in cognition and global function in patients with AD. Its clinical efficacy and minimal side-effect profile are thought to be related to its specific inhibition of AChE in the areas of the brain, affected by the cholinergic deficit that typifies this disease. Assessment of the potential impact of hepatic dysfunction on the pharmacokinetic and adverse event profiles of Donepezil is of primary importance, as Donepezil is orally administered and subject to extensive first-pass metabolism. The methods of analysis, pharmacology, physical properties, and preparation are also presented in this chapter. © 2010 Elsevier Inc.