Pharmacological basis of drug therapy of Alzheimer's disease.

ABSTRACT

Alzheimer's disease is a progressive neurodegenerative disorder primarily manifesting as a loss of memory. Senile plaques and neurofibrillary tangles are the major histopathological alteration in the brain of Alzheimer's disease patients. A considerable deficiency of cholinergic neurons is a consistent finding in Alzheimer's disease. Therefore, many therapeutic strategies to augment cerebral concentration of acetylcholine such as cholinergic precursors, cholinergic receptor agonists, cholinesterase inhibitors and acetylcholine release modulators have been evaluated in Alzheimer's disease. Although cholinesterase inhibitors such as tacrine and galanthamine offer modest clinical benefits, other cholinergic agents have proved to be of limited therapeutic value. Efforts to enhance monoaminergic neurotransmission have also been largely disappointing. Therefore, emphasis is not being put on the use of combination of two class of drugs. Moreover, use of therapeutic agents based on the putative pathogenic etiology of the disease such as excitotoxicity, amyloidosis, aluminium accumulation, inflammatory mechanisms and free radical production is being evaluated. Desferrioxamine, non-steroidal anti-inflammatory drugs, prednisone, dapsone, vitamin E and idebenone are some such agents that are currently under investigation for the preventive or palliative effect in Alzheimer's disease. Neurotrophic factors such as nerve growth factor, brain derived neurotrophic factor and epidermal growth factor have shown promising results in animal studies. However, novel methods for delivering these molecules into the brain required to be developed before launching their clinical trials in man.