SB-649868 explained

SB-649868 is a dual orexin receptor antagonist that was being developed by GlaxoSmithKline as a treatment for insomnia.^[1]

A phase I clinical trial evaluated doses up to 80 mg, resulting in significant improvement in sleep latency without adverse effects.^[2] In randomized, double-blind, placebo-controlled crossover trials, the 10 and 30 mg doses increased sleep time and reduced sleep latency.^[3] The subsequent phase II study added a 60 mg dose and observed dose-dependent sleep promotion.^[4]

The compound no longer appears to be under active development, with the last study posted to ClinicalTrials.gov completed in 2010.

See also

• Almorexant
• Filorexant
• Lemborexant
• Suvorexant

Further reading

• Web site: Psychiatry: An Innovative Drug Discovery Pipeline . GSK Neurosciences seminar . December 13, 2007 . Ratti E . https://web.archive.org/web/20081205182150/http://www.gsk.com/investors/presentations/2007/neurosciences-seminar-dec07/emiliangelo-ratti.pdf . December 5, 2008 .
• Scammell TE, Winrow CJ . Orexin receptors: pharmacology and therapeutic opportunities . Annual Review of Pharmacology and Toxicology . 51 . 243–66 . February 2011 . 21034217 . 3058259 . 10.1146/annurev-pharmtox-010510-100528 .

Notes and References

1. Renzulli C, Nash M, Wright M, Thomas S, Zamuner S, Pellegatti M, Bettica P, Boyle G . 6 . Disposition and metabolism of [14C]SB-649868, an orexin 1 and 2 receptor antagonist, in humans . Drug Metabolism and Disposition . 39 . 2 . 215–27 . February 2011 . 21045199 . 10.1124/dmd.110.035386 . 1995624 .
2. Bettica P, Nucci G, Pyke C, Squassante L, Zamuner S, Ratti E, Gomeni R, Alexander R . 6 . Phase I studies on the safety, tolerability, pharmacokinetics and pharmacodynamics of SB-649868, a novel dual orexin receptor antagonist . Journal of Psychopharmacology . 26 . 8 . 1058–70 . August 2012 . 21730017 . 10.1177/0269881111408954 . 29578953 .
3. Bettica P, Squassante L, Groeger JA, Gennery B, Winsky-Sommerer R, Dijk DJ . Differential effects of a dual orexin receptor antagonist (SB-649868) and zolpidem on sleep initiation and consolidation, SWS, REM sleep, and EEG power spectra in a model of situational insomnia . Neuropsychopharmacology . 37 . 5 . 1224–33 . April 2012 . 22237311 . 3306884 . 10.1038/npp.2011.310 .
4. Bettica P, Squassante L, Zamuner S, Nucci G, Danker-Hopfe H, Ratti E . The orexin antagonist SB-649868 promotes and maintains sleep in men with primary insomnia . Sleep . 35 . 8 . 1097–104 . August 2012 . 22851805 . 3397789 . 10.5665/sleep.1996 .