Preparation and affinity profile of novel nicotinic ligands

Novel nicotinic ligands, characterized by the presence of an amino substituted cyclopropane ring connected to a pyridine nucleus, are described. Pharmacological investigation revealed that these compounds exhibit highest affinity for the rat α4β2 subtype of the nicotinic receptor with no affinity for the muscarinic receptor. No appreciable affinity for the muscular or for the ganglionic nicotinic receptor was observed at concentrations up to 10 μM. The increase in cortical ACh release as well as a positive effect on memory in a social recognition test in rat are exemplified.

New nicotinic ligands with restricted conformational mobility induced by a cyclopropane ring are disclosed. Affinity studies indicated that these compounds are potent and selective α4β2 nicotinic ligands.Figure optionsDownload as PowerPoint slide