[Development of therapies for Alzheimer's disease based on cholinergic hypothesis-status quo and future directions]

Numerous approaches have been explored to treat individuals with Alzheimer's disease (AD). General approaches include the following treatment; treatment of cognitive symptoms, slowing decline, delaying onset of disease, and primary prevention. 2011 is the new era for the drug therapy for AD in Japan, because three anti-dementia drugs, galantamine, rivastigmine and memantine, were admitted to use for AD in addition to donepezil. Donepezil, galantamine and rivastigmine has been developed based on cholinergic hypothesis that acetylcholine (ACh) acts a chief neurotransmitter as a cognitive neurotransmitter. Donepezil a specific acetylcholinesterase inhibitor (AChEI). Galantamine acts as an allosteric potentiating ligand of nicotinic acetylcholine receptors in addition to the function of AChEI. Rivastigmine increase acetylcholine in the cholinergic synapse by inhibition of both AChE and butyrylcholinesterase. Recent study shows that these anti-dementia drugs afford symptomatic effect and also act as disease-modifiers which inhibit neuronal death and abnormal amyloid-beta deposition. These effects can slow the rate of decline of the disease. While in the past many of our attempts have been to treat secondary symptoms or improve the cognitive deficits, future attempts are likely to focus on slowing the rate of decline, delaying the onset of appearance, or preventing the disease.