Orexin receptor antagonists: a review of promising compounds patented since 2006

Expert Opin Ther Pat. 2010 Mar;20(3):307-24. doi: 10.1517/13543770903567085.


Importance of the field: The orexin neuropeptide system plays a central role in maintaining arousal and wakefulness. It has been demonstrated that small molecule antagonists to the orexin receptors promote sleep in preclinical species and in patients with insomnia.

Areas covered in this review: This review provides a summary of published patent applications claiming novel orexin antagonists from 2006 to mid-2009, covering both selective and dual orexin receptor antagonists.

What the reader will gain: Readers will gain an overview of orexin biology focusing on genetic and pharmacological validation of this target for treating sleep disorders. Additionally, this review discusses the importance of receptor subtype selectivity and the potential role of subtype selective and dual orexin antagonists in treating psychiatric illnesses beyond insomnia. This review identifies companies that are significant contributors to the patent literature claiming novel orexin receptor antagonists.

Take home message: The study of the orexin system has emerged as one of the key new fields of investigation in neuroscience. The demonstration of clinical proof-of-concept for the treatment of primary insomnia by Actelion in early 2007 has spurred significant interest in this field and competition has markedly increased since 2006.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems
  • Drug Evaluation, Preclinical
  • Humans
  • Hypnotics and Sedatives / pharmacology*
  • Mental Disorders / drug therapy
  • Mental Disorders / physiopathology
  • Orexin Receptors
  • Patents as Topic
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, Neuropeptide / antagonists & inhibitors*
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / physiopathology


  • Hypnotics and Sedatives
  • Orexin Receptors
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide