Author/Authors :
Simon N. Haydar، نويسنده , , Chiara Ghiron، نويسنده , , Laura Bettinetti، نويسنده , , Hendrick Bothmann، نويسنده , , Thomas A. Comery، نويسنده , , John Dunlop، نويسنده , , Salvatore La Rosa، نويسنده , , Iolanda Micco، نويسنده , , Martina Pollastrini، نويسنده , , Joanna Quinn، نويسنده , , Renza Roncarati، نويسنده , , Carla Scali، نويسنده , , Michela Valacchi، نويسنده , , Maurizio Varrone، نويسنده , , Riccardo Zanaletti، نويسنده ,
Abstract :
Alpha 7 nicotinic acetylcholine receptor (α7 nAChR) agonists are promising therapeutic candidates for the treatment of cognitive impairment associated with a variety of disorders including Alzheimer’s disease and schizophrenia. Alpha 7 nAChRs are expressed in brain regions associated with cognitive function, regulate cholinergic neurotransmission and have been shown to be down regulated in both schizophrenia and Alzheimer’s disease. Herein we report a novel, potent small molecule agonist of the alpha 7 nAChR, SEN12333/WAY-317538. This compound is a selective agonist of the α7 nAChR with excellent in vitro and in vivo profiles, excellent brain penetration and oral bioavailability, and demonstrates in vivo efficacy in multiple behavioural cognition models. The SAR and biological evaluation of this series of compounds are discussed.
Keywords :
Neuronal nicotinic acetylcholine receptors , Nicotinic ligands , Cognition , Auditory sensory gating
