Dissociating the pro‐cognitive effects of donepezil and an M1 PAM

Donepezil, an FDA approved drug for dementia in Alzheimer’s disease, increases the extracellular concentration of acetylcholine non‐selectively stimulating cholinergic receptors indiscriminately leading to dose‐limiting side effects. Muscarinic M1 sub‐receptor specific positive allosteric modulators (PAMs) have shown promise in addressing symptoms in Alzheimer’s disease, Schizophrenia and more1. M1 PAMs have little to no agonistic properties, avoiding peripheral side effects, and are mostly centrally located allowing for the modulation of endogenous signaling of the brain2.