A Comprehensive Review of Daridorexant, a Dual-Orexin Receptor Antagonist as New Approach for the Treatment of Insomnia

Molecules. 2022 Sep 16;27(18):6041. doi: 10.3390/molecules27186041.

Abstract

Insomnia affects 4.4-4.8% of the world's population, but because the effect of hypnotic drugs is limited and may cause harmful side-effects, scientists are turning their attention to developing drugs that act on the orexin system. Daridorexant, a selective dual-orexin receptor antagonist (DORA), has exhibited promising results in both animal and human studies. Its activity was evaluated based on the physiology-based pharmacodynamic and pharmacokinetic model. The use of daridorexant is considered safe, with no clinically significant side-effects including deprivation of next-morning residual effects. In this manuscript we conducted a comprehensive review of daridorexant including pharmacodynamics, animal and human research, pharmacokinetics and safety.

Keywords: DORA; daridorexant; insomnia; orexin antagonists; orexin system.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Hypnotics and Sedatives / pharmacology
  • Hypnotics and Sedatives / therapeutic use
  • Imidazoles
  • Orexin Receptor Antagonists* / pharmacology
  • Orexin Receptor Antagonists* / therapeutic use
  • Orexins
  • Pyrrolidines
  • Sleep Initiation and Maintenance Disorders* / drug therapy

Substances

  • Hypnotics and Sedatives
  • Imidazoles
  • Orexin Receptor Antagonists
  • Orexins
  • Pyrrolidines
  • daridorexant

Grants and funding

Funding number: DS 23/22 Grazyna Biala, Founder: Statutory Funds of the Medical University of Lublin, Poland.