Abstract
The systematic development of Alzheimer Disease (A.D.) therapy is only ten year old. It was initiated on a large scale following the publication in New England Journal of Medicine of the first successful results obtained with the cholinesterase inhibitor (ChEI) tacrine, (THA, tetrahydroaminoacridine) by Summers et al. (1986). Numerous studies (cf. Becker et al. 1991) had been performed previously, particularly in USA, in small groups of patients, with physostigmine (physo) alone or in combination with lecithine. Physostigmine, like tacrine, showed definite but only shortlasting improvements of cognitive symptoms (attention, concentration, memory) which were accompanied with severe peripheral and central cholinergic side effects. These consisted mainly of gastro-intestinal symptoms and drowsiness but in the case of tacrine also of liver toxicity. Physostigmine and tacrine represent important milestones in AD therapy as they supported in the patient, the pharmacological hypothesis formulated in the experimental animal (Mattio et al. 1986; Giacobini, 1987; Hallak and Giacobini, 1986; Giacobini et al. 1986) that a treatment improving function of the central cholinergic system obtained through an increase of brain ACh would also improve cognition in AD patients. Targeting the cholinergic system for AD therapy does not necessarily limit itself to use a cholinesterase inhibitor (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). A second, non-cholinergic approach, is based on the classic pathological landmarks of the disease aiming to decrease beta-amyloid (beta-A4) deposition and amyloidogenic APP (Amyloid Precursor Protein) release in brain (Fig 1).
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Giacobini, E. (1997). Alzheimer Disease. In: Filogamo, G., Vernadakis, A., Gremo, F., Privat, A.M., Timiras, P.S. (eds) Brain Plasticity. Advances in Experimental Medicine and Biology, vol 429. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9551-6_17
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