alpha7 nicotinic receptor partial agonism

Every compound in the sci-wiki that affects alpha7 nicotinic receptor partial agonism; the ones you can source are floated to the front, then the reference-only entries. Tap any for the full entry, mechanism, and outlets.

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Nootropic

AQW051

AQW051 was Novartis's alpha7 nicotinic acetylcholine receptor partial agonist, developed alongside ABT-126, TC-5619, and encenicline in the industry-wide push to translate the alpha7 receptor's role in hippocampal and prefrontal circuits into a working schizophrenia cognition drug. Novartis took an unusually mechanistic approach to testing it, using functional MRI in a randomized crossover trial to watch how the drug changed brain activation during working-memory and episodic-memory tasks in people with chronic, stable schizophrenia, rather than relying on behavioral scores alone. The imaging trial found AQW051 did alter neuronal activity in prefrontal and hippocampal regions, but it did not translate into a consistent cognitive benefit, and in smokers at higher doses working memory performance seemed to get worse rather than better. Combined with the broader wave of alpha7 agonist failures across the industry, Novartis did not carry AQW051 forward into larger confirmatory trials.

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Nootropic

TC-5619

TC-5619 was Targacept's alpha7 nicotinic acetylcholine receptor partial agonist, one of the most closely watched compounds of the alpha7-for-schizophrenia wave that swept through pharma in the early 2010s. An initial exploratory Phase II trial, run as an add-on to quetiapine or risperidone in schizophrenia outpatients, found statistically significant improvement on both a spatial-learning task (the Groton Maze Learning Task) and negative symptoms (SANS), enough of a signal that Targacept and its partner AstraZeneca pushed forward into a much larger, 477-patient, six-country Phase II trial. That bigger confirmatory study failed to replicate the earlier benefit, joining ABT-126, AQW051, and encenicline in the broader collapse of the alpha7 nicotinic hypothesis for schizophrenia cognition; AstraZeneca and Targacept discontinued the program not long after, and Targacept itself later folded into Catalyst Biosciences.

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