RT Journal Article SR Electronic T1 OREX-1019: a novel treatment for opioid use disorder and relapse prevention JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP jpet.119.261511 DO 10.1124/jpet.119.261511 A1 David R Maguire A1 Lisa R Gerak A1 Gerta Cami-Kobeci A1 Stephen M Husbands A1 Charles P. France A1 Barbara Belli A1 Peter Flynn YR 2019 UL http://jpet.aspetjournals.org/content/early/2019/11/20/jpet.119.261511.abstract AB There is an urgent need for new pharmacological treatments for substance use disorders, particularly for use in relapse prevention. A combination of buprenorphine with naltrexone has shown particular promise, with clinical studies indicating a substantial improvement over treatment with naltrexone alone. OREX-1019 (formerly BU10119) is a compound that mimics the pharmacology of the buprenorphine/naltrexone combination. This study evaluated the therapeutic potential of OREX-1019 for treating opioid use disorder. Pretreatment with OREX-1019 (0.01-0.3 mg/kg) dose-dependently decreased responding for the mu opioid receptor agonist remifentanil in rhesus monkeys but did not maintain levels of responding above vehicle when it was available for self-administration. OREX-1019 (0.01-1.0 mg/kg) also decreased cue- plus heroin-primed reinstatement of extinguished responding in monkeys that self-administered remifentanil but did not alter cue- plus cocaine-primed reinstatement of responding in monkeys that self-administered cocaine. OREX-1019 (0.3 mg/kg), like naltrexone (0.1 mg/kg), increased heart rate and blood pressure, produced overt observable signs, and eliminated food-maintained responding in monkeys treated chronically with morphine. These results confirm that OREX-1019 has little or no efficacy at mu opioid receptors and no abuse potential, and combined with promising safety and pharmacokinetic data, suggest it could be a safe and effective alternative to current treatments for opioid use disorders particularly as applied to relapse prevention.SIGNIFICANCE STATEMENT The novel opioid OREX-1019 potentially provides an improved relapse prevention agent for use in opioid use disorder. The current study demonstrates that in monkeys OREX-1019 is able to inhibit the self-administration of, and cue- plus drug-primed reinstatement of, responding for remifentanil.