Beyond tacrine - Recently developed cholinesterase inhibitors for the treatment of Alzheimer's disease

Alzheimer's disease still remains a diagnosis of exclusion. Until treatment strategies aimed at targeting its underlying aetiology become available, a cholinergic approach appears to be the most promising treatment for improving cognition in this devastating disease. Research to date suggests that cholinesterase inhibitors (ChEIs) produce only modest, if any, improvement in cognition. However, this class of drugs could be of greater interest if they slow the rate of deterioration in Alzheimer's disease compared with placebo-treated patients. The ChEIs tacrine and donepezil are to date the only drugs approved by the US Food and Drug Administration (FDA) for use in Alzheimer's disease. Donepezil is a long-acting drug and does not exhibit the adverse events, especially hepatotoxicity, associated with tacrine. The safety and tolerability features and efficacy of several other investigational drugs including metrifonate, rivastigmine (ENA 713), eptastigmine, galantamine (galanthamine) and huperzine A are being studied to evaluate their use in the management of patients with Alzheimer's disease.