Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
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, nicotine has significant side effects, including tachycardia, elevated blood pressure, and gastrointestinal distress. Agonists with better selectivity for nAChR subtypes that mediate the beneficial effects could be useful. Agonist binding to the α4β2 nAChR has been shown promote sAPPα secretion and attenuate Aβ production (Mousavi and Hellström-Lindahl, 2009).
Clinical Trial Timeline
- Sahakian B, Jones G, Levy R, Gray J, Warburton D. The effects of nicotine on attention, information processing, and short-term memory in patients with dementia of the Alzheimer type. Br J Psychiatry. 1989 Jun;154:797-800. PubMed.
- Mousavi M, Hellström-Lindahl E. Nicotinic receptor agonists and antagonists increase sAPPalpha secretion and decrease Abeta levels in vitro. Neurochem Int. 2009 Mar-Apr;54(3-4):237-44. PubMed.
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