Therapy Type: Small Molecule
Target Type: Cholinergic System
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: AstraZeneca, Targacept
Approved for: None
AZD1446 selectively activates the α4β2 subtype of nicotinic acetylcholine receptor.
Acute administration of nicotine to AD patients improved accuracy of delayed recall, as well as deficits in attention and information processing (Sahakian et al. 1989; Wesnes and Warburton, 1984; Jones et al, 1992). However, nictoine has significant side effects including tachycardia, elevated blood pressure, and gastrointestinal distress. Agonists with better selectivity for nAChR subtypes which mediate the beneficial effects could be useful. Agonit binding to the α4β2 nAChR has been shown promote sAPPα secretion and attenuate Aβ production (Mousavi & Hellström-Lindahl, 2009).
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