ARTICLE | Distillery Therapeutics

Therapeutics: Orexin 1 receptor (HCRTR1; OX1R)

February 12, 2015 8:00 AM UTC

Rat studies suggest a brain-penetrating OX1R antagonist could help treat stress- and hyperarousal-associated psychiatric disorders such as panic. Previous chemical synthesis and in vitro testing identified an antagonist that selectively bound human OX1R with 3.6 nM affinity. In rats, subcutaneous delivery of the antagonist resulted in more than 90% brain OX1R occupancy within 15 minutes that lasted for 4 hours. In rats subjected to chemical- or environmental-induced psychological stress and panic, the antagonist decreased stress- and panic-related behaviors compared with vehicle, without altering sleep-wake states. Next steps could include evaluating the OX1R antagonist in additional rodent models of psychiatric disorders.

Merck & Co. Inc. markets the dual orexin receptor antagonist Belsomra suvorexant to treat insomnia...