Single and Multiple Dose Safety, Pharmacodynamics and Pharmacokinetics of Xanomeline, a Novel Muscarinic M1 Agonist in Healthy Male Subjects

Abstract

Xanomeline (LY246708/NNC-11-0232) is a potent and selective muscarinic cholinergic M1 receptor agonist which has been shown to cross the blood brain barrier in animals. Increasing central cholinergic activity may provide a rational approach to therapy of Alzheimer’s dementia, since physostigmine and other acetyl cholinesterase inhibitors have shown therapeutic promise in such patients. The non-specificity and side-effect profile of this class of drugs is however less than optimal. As the density of post synaptic M1 receptors in the cortex and hippocampus remains largely unchanged in Alzheimer’s patients it is predicted that a cerebrally bioavailable and specific muscarinic agonist will have therapeutic utility without undesirable side effects.