PRX-03140 + donepezil

**PRX-03140 + donepezil** is a combination treatment investigated for Alzheimer's disease. PRX-03140 is a highly selective, orally bioavailable partial agonist of the serotonin 4 (5-HT4) receptor (with approximately 18% intrinsic activity compared to serotonin), and also exhibits binding to Sigma-1 and Sigma-2 receptors. Its mechanism includes stimulation of acetylcholine release and production in the brain, and activation of the alpha-secretase pathway, which promotes the non-amyloidogenic processing of amyloid precursor protein, potentially slowing Alzheimer's progression. Donepezil is an acetylcholinesterase inhibitor that increases synaptic acetylcholine levels, widely used as symptomatic therapy in Alzheimer's disease. In combination, PRX-03140 has been shown in preclinical studies and clinical trials to potentiate the donepezil-induced increase in cortical acetylcholine levels, resulting in improved cognitive scores as measured by ADAS-cog versus placebo; patients receiving both drugs demonstrated a higher increase in acetylcholine and memory markers than with either alone[1][3][5]. The main indication explored is Alzheimer's disease, and the combination appeared well tolerated in short-term studies with no serious drug-related adverse events[1][3].

Other names

donepezil