Synonyms: RO5313534, MEM 3454
Chemical Name: N-[(3S)-1-azabicyclo[2.2.2]oct-3-yl]-1H-indazole-3-carboxamide hydrochloride
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Inactive)
RG3487 is a selective nicotinic alpha-7 receptor (α7nAChR) partial agonist. It also has properties of a serotonin 3 receptor antagonist. It has been tested in Alzheimer's disease and cognitive symptoms of schizophrenia. In vivo, RG3487 improves object recognition memory and reverses spatial learning deficits in age-impaired rats. RG3487 improved drug-induced deficits in the prepulse inhibition, or startle, model of sensorimotor gating, and reversed impairments in executive function tasks. (Wallace et al., 2011).
Roche licensed this therapeutic from Memory Pharmaceuticals Corp. In 2006, Memory Pharmaceuticals had announced positive preliminary cognitive data from a phase 1 trial of MEM 3454, and in 2007 announced positive phase 2a results from a 2-month proof-of-concept trial in 80 Alzheimer's patients (see company press release). In 2008, Roche and Memory Pharmaceuticals expanded the development program for Mem4354 and Roche acquired Memory Pharmaceuticals (see press release).
In 2009 and 2010, Roche ran a phase 2 dose-ranging study in 389 people with mild-to-moderate Alzheimer's disease compared 6 months of treatment with 1, 5, or 15 mg/day of RG3487 to placebo. This study assessed efficacy and safety of the compound added to donepezil. Results were not reported publicly.
Also in 2010, Roche conducted an open-label phase 1 study in 16 healthy adults to evaluate the effect of memantine on the pharmacokinetics, safety and tolerability of RO5313534 and vice versa.
Development of this drug has been discontinued. For details on clinical trials on this compound, see clincialtrials.gov
- Wallace TL, Callahan PM, Tehim A, Bertrand D, Tombaugh G, Wang S, Xie W, Rowe WB, Ong V, Graham E, Terry AV, Rodefer JS, Herbert B, Murray M, Porter R, Santarelli L, Lowe DA. RG3487, a novel nicotinic α7 receptor partial agonist, improves cognition and sensorimotor gating in rodents. J Pharmacol Exp Ther. 2011 Jan;336(1):242-53. PubMed.
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