Name:	AZD1446
Other Names:	TC-6683
Therapeutic Applications:	Mild to moderate Alzheimer Disease
Therapy Types:	Oral, small molecule
Mechanisms:	α4ß2 nicotinic (nAChR) receptor activator
Development Status:	investigational outside U.S.
FDA Phase:	Phase II/IIa/IIb
Role in Alzheimer's Disease:	AZD1446 selectively activates the α4ß2 specific subtype (alpha4beta2) of neuronal nicotinic receptor found on nerve cells throughout the central nervous system. AZD1446 may thus act in a mechanism similar to AZD3480, by enhancing the release of acetylcholine from the cortex and thereby be memory-enhancing. The α4ß2 nAChR has been shown to be involved in nicotinic ligands effects to both promote sAPPα release and attenuate Aβ production, and thereby augmenting the non-amyloidogenic APP processing (Mousavi & Hellström-Lindahl, 2009).
Companies:	AstraZeneca Pharmaceuticals LP, Targacept, Inc.
Notes:	NCT01125683, phase II to evaluate effects of AZD1446, placebo and donepezil in patients with mild to moderate Alzheimer's Disease is currently recruiting participants in Russia, with additional study locations in France, Ukraine. See AZD1446- NCT01125683. This record was updated September 14, 2010.

References

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 PMID: 19111588. Abstract