Synonyms: Champix™, Chantix™, Varenicline tartrate, CP-526,555, Alpha4 beta2 nicotinic receptor agonist
Chemical Name: 7,8,9,10-Tetrahydro-6,10-methano-6H-pyrazino[2,3-h]benzazepin
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Approved for: Smoking cessation
Varenicline is a medication approved in the United States and many other countries to aid smoking cessation. It is a partial agonist of the α4β2 subtype of the nicotinic acetylcholine receptor (nAChR). It also acts on α3β4 and α7 nACHRs. Acting as a partial agonist, varenicline stimulates the α4β2 receptor without producing the full effect of the nicotine ligand. Its competitive binding on these receptors blocks the ability of nicotine to stimulate the mesolimbic dopamine system, hence its indicated use. Varenicline also acts as an agonist at 5-HT3 serotonine receptors, which are thought to contribute to its mood-altering effects. Side effects of vareniclin include as changes in behavior, agitation, depressed mood, and suicidal ideation, both in people with and without pre-existing psychiatric conditions. Vareniclin is one of several α4β2 nACHRs agonists that have been tested as treatments for Alzheimer's disease.
In 2009 and 2010, Pfizer compared vareniclin to placebo in a six-week Phase 2 trial in 66 patients with mild to moderate Alzheimer's disease for its ability to improve cognition as measured by the ADAS-Cog. The multi-center trial was conducted in South Korea. The trial assessed varenicline's safety, tolerability, and ability to improve cognition as measured by the ADAS-Cog. Fifty-four people completed the trial. Varenicline did not improve cognition, nor did it have a benefit on most of the study's secondary outcomes. It did, however, worsen participants' neuropsychriatic state and caused gastrointestinal side effects. Development of varenicline for Alzheimer's therapy was discontinued in 2011. For results of this trial see clinicaltrials.gov.
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