DORA-12

DORA-12 is a dual orexin receptor antagonist (DORA), a class of small molecule drugs originally developed for the treatment of insomnia but recently investigated for their potential to reduce withdrawal-associated sleep disturbances and prevent relapse in opioid use disorder. DORA-12 blocks both orexin receptor 1 and orexin receptor 2, reducing the effects of the wake-promoting neuropeptide orexin. In preclinical studies, daily oral administration of DORA-12 in rats during oxycodone withdrawal improved circadian rhythm disturbances, normalized physiological activities such as activity level and food/water intake, and significantly reduced drug-seeking behavior upon re-exposure to drug-associated cues. These effects were linked to DORA-12's ability to prevent oxycodone-induced changes in orexin neuron numbers in the hypothalamus. DORA-12 is an experimental agent and is closely related mechanistically to FDA-approved DORAs such as suvorexant, but is not approved for use in humans.