Dementias pp 233-251 | Cite as

Pharmacotherapeutic Approach to the Treatment of Alzheimer Disease

  • E. Giacobini


A systematic attempt to develop drugs to treat Alzheimer disease (AD) was initiated on a large scale 10 years ago following publication in the New England Journal of Medicine of the first successful results obtained with the Cholinesterase inhibitor (ChEI) tacrine (THA, tetrahydroaminoacridine) by Summers et al. [1]. Tacrine is not the first ChEI to be tested clinically for treating AD. Numerous studies [2] had been performed previously, particularly in the USA, in small groups of patients, with physostigmine (physo) alone or in combination with lecithin. Physostigmine, like tacrine, showed definite but only short-lasting improvements in cognitive symptoms (attention, concentration, memory), which were accompanied with severe peripheral and central cholinergic side effects. These consisted mainly of gastrointestinal symptoms and drowsiness, but in the case of tacrine also of liver toxicity. It was soon realized that in spite of this first encouraging result, both physo and tacrine were far from an ideal drug for AD treatment. However, physo and tacrine represent important milestones in AD therapy, as they supported for the first time in the patient the pharmacological hypothesis formulated in the experimental animal [3, 4, 5, 6] that a treatment improving function of the central cholinergic system obtained through an increase in brain acetylcholine (ACh) would also improve cognition in AD patients. Targeting the cholinergic system for AD therapy does not necessarily limit itself to use of a ChEI. Two other classes of cholinergic drugs might represent valid alternatives, such as nicotinic and muscarinic agonists alone or in combination with ChEI (Fig. 1).


Alzheimer Disease Cholinesterase Inhibitor Alzheimer Disease Patient Muscarinic Agonist Amyloid Precursor Protein Processing 
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