P11467: An Orally-Active Acetylcholinesterase Inhibitor and α2-Adrenoceptor Antagonist for Alzheimer’s Disease

Alzheimer’s disease (AD) is a complex and multifaceted neurodegenerative disease characterized by cognitive and behavioral abnormalities. The primary cognitive deficit has been correlated with extensive cholinergic dysfunction and the efficacy of cholinergic therapies in this disease validates and supports the cholinergic hypothesis of AD (Weinstock, 1995). To date, tacrine has shown clinical efficacy in 20 to 30% of AD patients and remains the only acetylcholinesterase inhibitor (AChEI) to receive FDA approval for symptomatic treatment (Knapp et al., 1994). However, the limited efficacy of pure cholinergic therapies suggests that other neurochemical deficiencies are involved.