ACHE and Alzheimer disease: Indeed, donepezil, the ‘gold standard’ acetylcholinesterase inhibitor (AChEI) in the symptomatic treatment of AD, has been found to have significant σ1 binding affinity (IC50 of 29.1 nM) [220], and to exert its anti-amnestic and neuroprotective activities against Aβ toxicity through activation of the σ1 receptors [139,220,260].