Therapeutics

AZD1446

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Overview

Name: AZD1446
Synonyms: TC-6683
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

Background

AZD1446 selectively activates the α4β2 subtype of nicotinic acetylcholine receptor. 

Findings

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

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024
AstraZeneca NCT01039701
N=99
AstraZeneca NCT01125683
N=40

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References

Paper Citations

  1. . 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.
  2. . 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.

Further Reading

No Available Further Reading