Orexin is a neurotransmitter that regulates wakefulness and appetite. Orexins are excitatory neuropeptides that have a critical role in maintaining wakefulness. Orexin receptor antagonists promote sleep in animals and humans. Indeed, small molecule orexin receptor antagonists have demonstrated clinical proof-of-concept in the treatment of primary insomnia. This review describes optimization of orexin receptor antagonists across diverse structural classes with a focus on how molecules were designed to optimize potency, physicochemical properties, pharmacokinetics, brain penetration, and in vivo activity.
^Davis, Jon F.; Derrick L. Choi (Jan. 29, 2011). Preedy, Victor R., ed. Handbook of Behavior, Food and Nutrition. New York: Springer. pp. 321–2. ISBN978-0-387-92271-3.Check date values in: |date= (help)