“Given the increasingly recognized societal impact of substance abuse, and the lack of safe and effective therapies, we are very encouraged by the activity demonstrated by NYX-783 in these preclinical models of alcohol use disorder,” said
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 (p<0.0001 for both studies). 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 (p<0.001) or stress-associated cues in the stress-induced alcohol-seeking model (p<0.05). 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 (p<0.05).
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.
Poster Presentation Details:
Presentation Title: The Novel NMDAR Modulator NYX-783 Facilitates Extinction of Ethanol-seeking Behavior and Blocks Relapse-like Behavior Primed by Ethanol-associated Cues or Prior Stress in Rats (Poster Number: 039-732)
NYX-783 is a novel, oral NMDA receptor modulator currently in Phase 2 development for the treatment of post-traumatic stress disorder (PTSD). In preclinical studies of NYX-783, particularly strong results were observed in psychiatric models, models of fear extinction, and models of substance abuse. In a Phase 1 clinical study of NYX-783, ample central nervous system exposure was observed and the product candidate demonstrated a favorable safety and tolerability profile, with no serious adverse effects, across a wide dose range.
About Alcohol Use Disorder
Alcohol use disorder is a chronic, relapsing condition characterized by compulsive alcohol use, loss of control over alcohol intake, and a negative emotional state when not using alcohol. Alcohol use disorder affects an estimated 16 million people in
About Post-Traumatic Stress Disorder
More than eight million people in
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