Abstract

Development of novel therapies for Alzheimer's disease has now been given much attention, with an aim to search for more potent drugs for long term use through various approaches and hypothesis. Five distinct hypothesis/approaches for the therapies have been discussed in this review, namely, (1) cholinergic hypothesis, (2) hormone replacement approaches, (3) antiinflammatory approaches, (4) neurotrophic approaches and (5) an approach to inhibit formation of amyloid and neurofibrillary tangles. In the cholinergic hypothesis, acetylcholinestrase inhibitors have been more successful and potent compounds have been identified that include tacrine, physostigmine, donepezil and rivastigmine. Among these, tacrine and physostigmine have been associated with toxicity and bioavailability problems respectively and donepezil and rivastigmine have been launched in the market. Estrogen has shown efficacy in the treatment of Alzheimer's disease giving rise to the hormone replacement approach. Few antiinflammatory drugs such as ibuprofen, naproxen and rofecoxib have shown promise in long term therapy against Alzheimer's disease. Agents that stimulate neurotrophic effects such as citicoline, anapsos and AITS-C32 have shown progress in treatment of mental impairment and are at different stages of clinical trials. Few amino acid derivative, amine and urea analogs and hydorxy-hexamide have been shown to inhibit amyloid β synthesis or/and release.