The muscarinic M1 receptor positive allosteric modulator PQCA improves cognitive measures in rat, cynomolgus macaque, and rhesus macaque.

Rationale: The current standards of care for Alzheimer's disease, acetylcholinesterase inhibitors, have limited efficacy due to a host of mechanism-related side effects arising from indiscriminate activation of muscarinic and nicotinic receptors. The M1 muscarinic receptor is predominantly expressed in the brain in regions involved in cognition, and therefore selective activation of the M1 receptor would be expected to boost cognitive performance with reduced risk of peripheral side effects.

Objectives: Here we investigated whether the selective M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance and cerebral blood flow.