Alzheimer’s disease (AD) is the most common single cause of dementia. Alzheimer’s disease is a chronic syndrome of the central nervous system that causes a decline in cognitive function and language ability. The enzyme cholinesterase (ChE) is a significant therapeutic target for Alzheimer’s disease. The main cause of Alzheimer’s disease is the reduction in acetylcholine (ACh) synthesis. Therefore, one of the potential therapeutic strategies is to increase the cholinergic levels in the brain by inhibiting the biological activity of acetylcholinesterase (AChE). P11149 is a potent, competitive, and selective inhibitor of AChE.

AChE inhibitors can limit the degradation of ACh. AChE inhibitors are able to increase the function of neural cells by increasing the concentration of ACh. Moreover, β-amyloid is a proteolytic fragment from the amyloid precursor protein (APP). The progressive synthesis and aggregation of β-amyloid are additional critical factors involved in Alzheimer’s disease pathogenesis. In particular, AChE may directly interact with amyloid-beta in a manner that increases the deposition of this peptide into insoluble plaques. Additionally, cholinergic modulation and other functional consequences of AChE inhibition may affect amyloid precursor protein processing and protect neurons against a variety of insults.

Acetylcholinesterase (AChE) inhibitors from several chemical classes have been tested for the symptomatic treatment of Alzheimer’s disease. P11149 is a potent, competitive, and selective inhibitor of AChE, demonstrating central cholinergic activity, behavioral efficacy, and safety.

P11149 significantly inhibits rat brain AChE. Furthermore, P11149 shows central cholinergic activity biochemically. Besides, P11149 causes hypothermia by attenuating scopolamine-induced deficits in passive avoidance. In addition, P11149 enhances step-down passive avoidance, another measure of behavioral efficacy.

G M Bores, et al. Pharmacological evaluation of novel Alzheimer’s disease therapeutics: acetylcholinesterase inhibitors related to galanthamine. J Pharmacol Exp Ther. 1996 May;277(2):728-38.