Mechanism of CNS Drugs and their Combinations for Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. To date, there is no cure for this disease. The FDA approved drugs, cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine) and an N-methyl-Daspartate receptor antagonist (memantine) for the treatment of AD are symptomatically effective to some patients for short periods of time. Cholinesterase inhibitors exert additional pharmacological action beyond inhibition of cholinesterase that may maximize and prolong the effective of these drugs. The complexity of AD pathogenesis limits these drugs to correct every aspect of the disease. This problem has led to the current challenge in drug discovery to develop multitarget or combinational therapy. EGb 761 is a standardized extract of Ginkgo biloba leaves and has been shown to have potential benefit effects in various models of AD. Combination drug therapy, the use of drugs that act at different targets, may offer a novel strategy for management of AD. In this review, we evaluate mechanisms of individual drugs for treatment of AD and summarize the combination studies between cholinesterase inhibitors and NMDA receptor antagonist memantine, cholinesterase inhibitors and EGb 761 in experimental models and clinical trials.