Identification of Psychoplastogenic Tropanes Lacking Muscarinic Activity
Hunter T Warren, Winston L. Chow, Milan Chytil, Kurt Rasmussen, David E. Olson
Journal of Medicinal Chemistry July 9, 2024 DOI: 10.1021/acs.jmedchem.4c01204 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Phenotypic structure-activity relationship study Peer reviewed |
|---|---|
| Keywords | Muscarinic acetylcholine receptor Identification biology Pharmacology Biochemistry Genetic neurodegenerative diseases |
| Citations | 5 |
| Key points | Novel tropanes were found that promote cortical neuronal growth with drastically reduced muscarinic receptor activity compared to scopolamine. |
Abstract
Tropane-containing small molecules like scopolamine are a promising class of psychoplastogens. However, their potent antagonism of all muscarinic receptor subtypes presents the potential for undesirable anticholinergic side effects. In an effort to decouple their neuroplasticity-promoting effects from their muscarinic activity, we performed phenotypic structure-activity relationship studies across a variety of structurally distinct subclasses of tropanes. We discovered several novel tropanes capable of significantly increasing cortical neuronal growth while exhibiting drastically reduced activity at all muscarinic receptor subtypes compared to scopolamine.