Serotonin 5-HT(2A) receptor antagonists in the treatment of insomnia: present status and future prospects.
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.
Monti
J M
JM
Department of Pharmacology and Therapeutics, School of Medicine Clinics Hospital, Montevideo, Uruguay. jmonti@mednet.org.uy
D000328:Adult; D000818:Animals; D001569:Benzodiazepines / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000627:therapeutic use; D012701:Serotonin / Q000378:metabolism; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D012890:Sleep / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000453:epidemiology
D006993:Hypnotics and Sedatives; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D001569:Benzodiazepines; D012701:Serotonin