Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5554564 | European Journal of Pharmacology | 2017 | 11 Pages |
Abstract
The α7 nicotinic acetylcholine receptor is thought to play an important role in human cognition. Here we describe the in vivo effects of BMS-902483, a selective potent α7 nicotinic acetylcholine receptor partial agonist, in relationship to α7 nicotinic acetylcholine receptor occupancy. BMS-902483 has low nanomolar affinity for rat and human α7 nicotinic acetylcholine receptors and elicits currents in cells expressing human or rat α7 nicotinic acetylcholine receptors that are about 60% of the maximal acetylcholine response. BMS-902483 improved 24 h novel object recognition memory in mice with a minimal effective dose (MED) of 0.1 mg/kg and reversed MK-801-induced deficits in a rat attentional set-shifting model of executive function with an MED of 3 mg/kg. Enhancement of novel object recognition was blocked by the silent α7 nicotinic acetylcholine receptor agonist, NS6740, demonstrating that activity of BMS-902483 was mediated by α7 nicotinic acetylcholine receptors. BMS-902483 also reversed ketamine-induced deficits in auditory gating in rats, and enhanced ex vivo hippocampal long-term potentiation examined 24 h after dosing in mice. Results from an ex vivo brain homogenate binding assay showed that α7 receptor occupancy ranged from 64% (novel object recognition) to ~90% (set shift and gating) at the MED for behavioral and sensory processing effects of BMS-902483.
Related Topics
Life Sciences
Neuroscience
Cellular and Molecular Neuroscience
Authors
Rick L. Pieschl, Regina Miller, Kelli M. Jones, Debra J. Post-Munson, Ping Chen, Kimberly Newberry, Yulia Benitex, Thaddeus Molski, Daniel Morgan, Ivar M. McDonald, John E. Macor, Richard E. Olson, Yukiko Asaka, Siva Digavalli, Amy Easton,