The Hybrid Approach for Nicotinic Acetylcholine Receptor (nAChR) Ligands
Nicotinic acetylcholine receptors (nAChRs) are involved in multifarious central nervous system (CNS) disorders. There is a high demand for better CNS drugs in the future because of an enormous increase in psychiatric and neurodegenerative disorders along with the often disappointing efficacy in treating these diseases. Since CNS diseases are most likely originated in the dysfunction of a dynamic network of interacting biological targets, we are interested to develop compounds with multiple modes of action (“desired polypharmacology”) with the goal to enhance efficacy for the treatment of mood and neurodegenerative disorders. The challenge is to combine the desired pharmacological effects in one compound with drug-like physicochemical properties. A DML would also enhance patient compliance and reduce metabolic and safety issues.
This project will lay the foundation for nAChR related hybrid compounds or DMLs (designed multiple ligands) for the development of potential therapeutics for the treatment of mood and neurodegenerative disorders.