Aptinyx presents preclinical data on NYX-783 in alcohol-seeking behavior
Aptinyx announced the presentation of preclinical data on its novel NMDA receptor modulator, NYX-783, demonstrating that the product candidate robustly attenuated alcohol-seeking and relapse-like behavior in multiple models of alcohol use disorder. These studies were conducted in collaboration with the Medical University of South Carolina and data are being exhibited in a poster presentation today at the 42nd Annual Research Society on Alcoholism Scientific Meeting in Minneapolis, Minnesota. In the studies being presented, behavior was assessed in two different models of alcohol use disorder in which animals were trained to self-administer ethanol through lever pressing. In the first model, an alcohol dependence model, alcohol dependence was induced in rats by exposing animals to ethanol vapor, with exposure to air used as a comparative control. After alcohol dependence was established, rats were dosed with either 0.1 mg/kg NYX-783, 6 mg/kg NYX-783, or vehicle one hour prior to the first extinction session. During the extinction sessions, animals were exposed to cues previously associated with alcohol intake, however lever pressing no longer resulted in alcohol delivery. Extinction was measured by the number of days to achieve elimination of alcohol-seeking behavior. Three weeks after extinction, rats were evaluated for relapse-like behavior after re-exposure to alcohol associated cues. In the second model, a stress-induced alcohol-seeking model, rats were exposed to a stressor prior to being trained to self-administer ethanol. Stress exposure increased alcohol-seeking behavior and rendered rats resistant to extinction of alcohol-seeking behavior. This approach models the influence of PTSD on substance abuse. Animals were then evaluated during and after the same extinction paradigm as described in the alcohol dependence model.In both the alcohol dependence model and the stress-induced alcohol seeking model, animals dosed with NYX-783 prior to extinction demonstrated a significantly more rapid elimination of alcohol-seeking behavior as compared to vehicle. Animals dosed with NYX-783 prior to extinction also demonstrated significantly less relapse-like behavior when exposed to alcohol-associated cues in the alcohol dependence model or stress-associated cues in the stress-induced alcohol-seeking model. In the stress-induced alcohol seeking model, animals that were only dosed with NYX-783 prior to re-exposure to the stress-associated cue also demonstrated significantly less relapse-like behavior when compared to vehicle-treated rats. The data being presented support the continued evaluation of NYX-783 in human clinical studies and indicate that treatment with NYX-783 may be an effective approach to addressing alcohol abuse in patients with or without comorbid PTSD.