Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
Company: TorreyPines Therapeutics, Inc.
Approved for: None
Hypo-activity of the cholinergic system is associated with AD and cognitive decline. Two different strategies have been used to increase cholinergic acitvity in the AD brain: 1) acetylcholinesterase inhibitors and 2) direct stimulation of cholinergic receptors. NGX267 is a selective agonist at the M1 muscarinic acetylcholine receptor. Like other M1 agonists such as AF102B (cevimeline), AF267B has been shown to increase αAPPs, decrease Aβ levels and tau hyperphosphorylation, and block Aβ-induced neurotoxicity in vitro via M1 receptor-mediated modulation of kinases (e.g. PKC, MAPK and GSK3β) (reviewed in Fisher, 2007).
AF267B was found to improve spatial memory in 3xTg-AD mice and was associated with reduced Aβ and tau pathology in the hippocampus and cortex (Caccamo et al., 2006).
- Caccamo A, Oddo S, Billings LM, Green KN, Martinez-Coria H, Fisher A, Laferla FM. M1 receptors play a central role in modulating AD-like pathology in transgenic mice. Neuron. 2006 Mar 2;49(5):671-82. PubMed.
- Fisher A. M1 muscarinic agonists target major hallmarks of Alzheimer's disease--an update. Curr Alzheimer Res. 2007 Dec;4(5):577-80. PubMed.
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