New nicotinic analogue ZY-1 enhances cognitive functions in a transgenic mice model of Alzheimer's disease.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive loss of memory and cognitive function. One of the new approaches for treating AD is direct stimulation of nicotinic acetylcholine receptors (nAChRs) in the brain. α4ß2-nAChR agonists have shown promising potential in preclinical cognition models of AD. The present report describes the pharmacological properties of ZY-1, a new nicotinic analogue that activates α4ß2-nAChR. We describe in detail the binding profile and pharmacological effects of ZY-1 on transgenic AD mice. ZY-1 has high affinity to α4ß2-nAChR. In a Morris water maze test, ZY-1 significantly decreases the escape latency and increases both the times in the platform quadrant and the times of platform crossing of transgenic mice. ZY-1 enhances cognitive functions in transgenic mice models of AD. As a novel nicotinic analogue, ZY-1 deserves further study as a potential candidate against AD.