Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia.

摘要: Since its discovery in 1998, the orexin system, composed of two G-protein coupled receptors, orexins 1 and 2, neuropeptide agonists, A B, has captured attention scientific community as a potential therapeutic target for treatment obesity, anxiety, sleep/wake disorders. Genetic evidence rodents, dogs, humans was revealed between 1999 2000, demonstrating causal link dysfunction or deletion system narcolepsy, disorder characterized by hypersomnolence during normal wakefulness. These findings encouraged efforts to discover agonists treat narcolepsy and, alternatively, antagonists insomnia. This perspective will focus on development structurally diverse suitable preclinical pharmacology studies human clinical trials. The work described herein culminated 2014 FDA approval suvorexant first-in-class dual receptor antagonist