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Evaluating Highly Selective Nicotinic Receptor Agonists and Antagonists

Institution: California Institute of Technology
Investigator(s): Dennis Dougherty,
Award Cycle: 2019 (Cycle 29) Grant #: T29IR0445 Award: $1,227,300
Subject Area: Neuroscience of Nicotine Addiction and Treatment
Award Type: High Impact Research Project Award

Initial Award Abstract
An established smoking cessation therapeutic strategy is to develop molecules that can interact with nicotinic receptors in the brain, thereby blocking the actions of nicotine, preventing nicotine addiction and promoting quitting. However, different types of nicotinic receptors are present in different regions of the brain and also in other organs, making it difficult to develop molecules that are effective in the correct parts of the brain, while not causing unwanted effects elsewhere. Current cessation products have met with limited success, including low long-term abstinence success rates and sometimes severe side effects. Using unique molecular and computational tools to study the precise binding of nicotine and other molecules (potential cessation products) with the various types of nicotinic receptors, this work will lead to the development of a new generation of more potent, more selective compounds that target the desired nicotinic receptors. This in turn will lead to safer, more effective smoking cessation strategies.