Orexin receptor antagonists – a patent review (2010 to August 2014)

Abstract

Introduction: The orexin (hypocretin) system is an evolutionarily conserved neuropeptide-G-protein-coupled receptor system, consisting of two neuropeptides the orexin-A and the orexin-B peptides as well as two receptors the orexin-1 and the orexin-2 receptors. The orexin system is crucially involved in the regulation of the circadian rhythm, states of wakefulness and arousal and the modulation of emotions and has attracted the interest of many researchers which resulted in an enormous amount of insight, mainly in the field of antagonists. Clinical proof of concept was obtained with dual orexin receptor antagonists in primary insomnia. Merck’s suvorexant got FDA approval on 13 August 2014 for the treatment of insomnia.

Areas covered: The patent applications from Thomson Reuters Integrity Database (covering 2010 – August 2014) are summarized, analyzed and discussed in the review.

Expert opinion: Intense patenting activities have been observed over the past 3 years in the field of orexin antagonists. Several compounds have been investigated in clinical trials mainly for the treatment of primary insomnia. The advantage of orexin antagonists, based on animal pharmacology results, is the promotion and maintenance of physiological sleep which should avoid hangover phenomena reported as side effects of approved treatments. Many other potential treatment options are mentioned for orexin antagonists of different selectivity profiles.

Keywords::

• addiction
• G-protein-coupled receptors
• insomnia
• neuropeptides
• orexin peptides
• orexin receptors
• sleep