ArticleNeuroscience applied2024
A novel, non-opioid, selective orexin-1 receptor antagonist for the treatment of substance use disorders.
Article in Neuroscience applied, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
There is a pressing need for novel treatments for substance use disorders to address increasing rates of addiction and drug overdose. Preclinical studies have shown that the orexin (hypocretin) system in the brain, mediated primarily by the orexin 1 receptor, plays a role in reward-related behaviours and that selective blockade of this receptor is efficacious in rodent models of addiction for a wide range of substances including opioids, cocaine, nicotine, and alcohol. We report here the preclinical profile of C4X3256, a novel, selective oral antagonist of the orexin 1 receptor. In the rat, high levels of receptor occupancy were observed in the tenia tecta region of the brain for up to 8 h following oral dosing. Translation of brain receptor occupancy into pharmacological efficacy was demonstrated in rat models showing significantly reduced nicotine self-administration and diminished cue-induced reinstatement of nicotine seeking following an oral dose of 30 mg/kg C4X3256. In addition, C4X3256 significantly reduced reinstatement of cocaine seeking induced by presentation of tone/light cues in a rat model of relapse. In summary, the nonclinical profile of C4X3256 has supported the progression of this compound into human clinical trials as an investigational medicinal product for the treatment of substance use disorders.
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