title: Current Phase II investigational therapies for insomnia.
abstract: BACKGROUND
  Insomnia is typified by a difficulty in sleep initiation, maintenance and/or quality (non-restorative sleep) resulting in significant daytime distress.
  
  
  METHODS
  This review summarizes the available efficacy and safety data for drugs currently in the pipeline for treating insomnia. Specifically, the authors performed MEDLINE and internet searches using the keywords 'Phase II' and 'insomnia'. The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT2A (ITI-007), melatonin/serotonin5-HT1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.
  
  
  CONCLUSIONS
  Low-priced generic environments and high development costs limit the further development of drugs that treat insomnia. However, the bidirectional link between sleep and certain comorbidities may encourage development of specific drugs for comorbid insomnia. New insomnia therapies will most likely move away from GABAAR receptors' modulation to more subtle neurological pathways that regulate the sleep-wake cycle.
authors.affiliation: Tel Aviv University, Department of Neurobiology, The George S Wise Faculty of Life Sciences , Tel Aviv 69978 , Israel +972 3 6409611 ; +972 3 6407643 ; navazis@post.tau.ac.il.
authors.forename: Nava
authors.initials: N
authors.lastname: Zisapel
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018757:GABA Modulators / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D015507:Drugs, Investigational; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A
keywords: GABA; drugs; histamine; insomnia; melatonin; orexin; receptors; serotonin