Focus on Donepezil - an anti dementia drugDonepezil hydrochloride is a piperidine that is a cholinesterase inhibitor (ChE inhibitor). Senile dementia of the Alzheimer type (SDAT) has been linked to losses of presynaptic choliergic function in the nucleus basalis of the brain. Cholinegic agents - either agonists or enzyme inhibitors have been put forward as therapeutic agents. Donepezil is one such candidate for a thereapeutic agent in SDAT.Donepezil hydrochloride is a selective, reversible and non-competitive acetylcholinesterase inhibitor with a relatively high central versus peripheral specificity. Acetylcholinesterase is the predominant cholinesterase in the brain. Plasma levels of donepezil and AChE inhibition are positively correlated until a plateau of inhibittion is reached at about 80% at donepezil levels of 50 ng/ml and above (Rogers et al, 1996). The loss of cholinergic neurons in the nucleus basalis of Meynert is one of the hallmarks of Alzheimer's disease. Animals with nucleus basalis lesions responded to donepezil and improved on learning and memeory tasks.
