Alzheimer's disease therapy - an update.
The 5th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy focused on new therapeutic approaches for the treatment of Alzheimer 's disease (AD) based on the latest basic science data. The two major pharmacological principles of cholinergic therapy are 1) reduction of acetylcholine hydrolysis by means of acetylcholinesterase (AChE) inhibitors; and 2) direct stimulation of nicotinic or muscarinic receptors with selective agonists. Currently used AChE inhibitors are tacrine, donepezil hydrochloride, rivastigmine and metrifonate. In the area of muscarinic and nicotinic receptor modulation, studies were presented on AF-102B and AF-150(S), BIBN-99, CI-1017, RJR-2403, ABT-418, ABT-089, GTS-21 and SIB-1553A. Based on evidence of inflammatory mechanisms in the pathogenesis of AD, selective COX-2 inhibitors for the prevention and treatment of AD are a target of several pharmaceutical companies. Concerning known antiinflammatory drugs, results from controlled trials are expected soon. Estrogen replacement has been reported to produce cognitive and affective improvement in women with AD, and results from a number of studies were presented. Age-associated increases in oxidative stress may play a role in AD and thus antioxidants may also have a place in the therapy of this disease. The antioxidants vitamin E and selegiline are being investigated. Other drugs under investigation are propentofylline, Cerebrolysin, citicoline sodium, CDP-choline, memantine, Egb-761, calagualine and AIT-082. Iododoxorubicin may represent a new class of compounds able to interfere with the beta-amyloid cascade in AD and other brain amyloid diseases. Future preventive strategies in AD include genotype analysis and screening, presymptomatic diagnosis and avoidance of environmental risk factors.
Nikolov
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Pharmacological Department, Chemical Pharmaceutical Research Institute, Sofia, Bulgaria.