Cognition Improvement by Oral Huperzine A: A Novel Acetylcholinesterase Inhibitor

Abstract

Alzheimer’s disease (AD) is one of the most severe mental health problems commonly found in the aged population. The dementia disorders will continue to constitute a major burden upon social and medical care systems due to the mean age of the population as it continues to rise. Hence, a cure or prevention for the disease would be most desirable. Current efforts to develop an effective drug treatment for AD are in large part based upon the consistent finding that patients with this disease suffer from marked reduction of cholinergic neuronal function resulting in a deficiency in acetylcholine (ACh) concentration in the central nervous system (Whitehouse et al., 1982; Davies and Maloney, 1976; Coyle et al., 1983), and that these reductions have been associated with changes in memory (Giacobini, 1991). Of all the attempts at symptomatic therapy for AD based on the cholinergic hypotheses, studies using cholinesterase inhibitor (ChEI) has been the most encouraging up to now (Pomponi et al., 1990). Several ChEIs such as physostigmine (Phys) (Thal, 1991) and tacrine (THA) (Summers et al., 1986) have recently been the focus of extensive clinical investigation in patients who had AD (Becker and Giacobini, 1988). However, the liver toxicity with a higher dose of THA and short duration of action as well as a narrow dosing range with Phys were viewed as serious limitations to the development of these compounds as therapeutics. At present there is no therapeutic ChEI that has been shown to be both effective and safe in the treatment of AD. Thus the search for a potent, long-acting ChEI which exerts minimal side effects in the clinic for the treatment of AD is still most active.

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