M1 receptor positive allosteric modulators discovery approaches
Takao Mandai, Arthur A. Simen, Antonio Laurenza, Haruhide Kimura · Trends in Pharmacological Sciences · 2025
The development of M1 muscarinic acetylcholine-receptor-positive allosteric modulators has been hindered by their limited cognitive efficacy and cholinergic side effects. We discuss two unique approaches - low intrinsic agonism and low binding cooperativity - that were developed to address these issues and their therapeutic implications.