Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity
Journal of Medicinal Chemistry July 9, 2024 Hunter T. Warren, Winston L. Chow, Milan Chytil et al. 5 citations
Tropane-containing small molecules such as scopolamine can promote neuronal growth (psychoplastogens) but also block all muscarinic receptor subtypes, causing unwanted anticholinergic side effects. Researchers conducted phenotypic structure-activity relationship studies on various tropane subclasses to separate these effects. They identified several novel tropanes that substantially increase cortical neuron growth while showing much weaker activity at all muscarinic receptor subtypes than scopolamine, suggesting that the neuroplasticity-promoting and muscarinic-blocking properties can be decoupled.