Serotonin 5-HT(2A) Receptor Antagonists in the Treatment of Insomnia: Present Status and Future Prospects

Drugs Today (Barc). 2010 Mar;46(3):183-93. doi: 10.1358/dot.2010.46.3.1437247.


Benzodiazepine (BZD) and non-BZD hypnotics improve sleep induction and sleep maintenance. BZD induces a further reduction of slow wave sleep (SWS) and rapid eye movement (REM) sleep, whereas SWS and REM values remain decreased during non-BZD administration. There is evidence indicating that the nonselective serotonin 5-HT(2A/2C) receptor antagonists, ritanserin, ketanserin, seganserin and ICI-169369, the selective 5-HT(2A) receptor antagonist eplivanserin and the 5-HT(2A) receptor inverse agonist pimavanserin, increase SWS in subjects with normal sleep. In addition, it has been shown that prior administration of ritanserin prevents the nitrazepam-induced suppression of SWS in normal subjects. Of note, ritanserin also induced an increase of SWS in poor sleepers, patients with chronic primary insomnia and psychiatric patients with a generalized anxiety disorder or a mood disorder. The 5-HT(2A) receptor inverse agonist APD-125 gave rise to a similar effect in patients with chronic primary insomnia. Thus, presently available evidence tends to indicate that the association of a 5-HT(2A) receptor antagonist or a 5-HT(2A) receptor inverse agonist with a BZD or a non-BZD hypnotic could be a valid alternative to normalize SWS in patients with primary or comorbid insomnia.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Benzodiazepines / therapeutic use
  • Humans
  • Hypnotics and Sedatives / pharmacology*
  • Hypnotics and Sedatives / therapeutic use
  • Serotonin / metabolism
  • Serotonin 5-HT2 Receptor Antagonists*
  • Serotonin Antagonists / pharmacology
  • Serotonin Antagonists / therapeutic use
  • Sleep / physiology
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Sleep Initiation and Maintenance Disorders / epidemiology


  • Hypnotics and Sedatives
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • Benzodiazepines
  • Serotonin