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Sleep-related disorders

Expanding the applications of clock-gene modulation

Nature Reviews Drug Discovery volume 14, pages 92–93 (2015)Cite this article

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Burris and colleagues began by investigating the effect of SR9011, a small-molecule REV-ERB agonist, on sleep and wakefulness in mice through use of electroencephalogram recordings. Relative to vehicle-treated control mice, mice injected intraperitoneally with the drug at a time when they would usually be asleep showed a considerable increase in wakefulness for 2 hours post-injection. Accordingly, slow-wave sleep and rapid eye movement (REM) sleep were reduced during this period. Drug-treated mice also showed increased locomotor activity as measured by telemetry. These effects were not observed if the drug was administered during their wakeful period.

Genetic findings in mice with polymorphisms in clock genes have suggested a link between disrupted circadian rhythms and psychiatric disorders such as depression and anxiety. Burris and co-workers therefore investigated the effect of SR9011 in various models of anxiety.

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References

  1. Banerjee, S. et al. Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. Nature Commun. 5, 5759 (2014)

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  1. Katie Kingwell
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Kojetin, D. J. & Burris, T. P. REV-ERB and ROR nuclear receptors as drug targets. Nature Rev. Drug Discov. 13, 197–216 (2014)

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Kingwell, K. Expanding the applications of clock-gene modulation. Nat Rev Drug Discov 14, 92–93 (2015). https://doi.org/10.1038/nrd4541

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