Positive Allosteric Modulators of Nicotinic Acetylcholine Receptors (nACh)

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated channels related to different pathologies, among others, Alzheimer’s disease, schizophrenia, cancer and pain. The search for modulators of these receptors has attracted considerable interest, especially the allosteric modulators that permit selective regulation and, at the same time, avoid many of the adverse effects associated with ligands that directly target the agonist binding site.

Recently, the high throughput screening (HTS) of a heterogeneous collection of small-molecules permitted the identification of a potent and selective positive allosteric modulator of the α7 nAChR. Starting from this compound, we have developed a new series of allosteric modulators of the a7 receptor channel. We are currently working on the optimization of this new series, searching for new compounds with improved therapeutic profile.