Effects of GF-015535-00, a novel α1 GABA A receptor ligand, on the sleep-wake cycle in mice, with reference to zolpidem.

Abstract

STUDY OBJECTIVES:

Novel, safe, and efficient hypnotic compounds capable of enhancing physiological sleep are still in great demand in the therapy of insomnia. This study compares the sleep-wake effects of a new α1 GABA(A) receptor subunit ligand, GF-015535-00, with those of zolpidem, the widely utilized hypnotic compound.

METHODS:

Nine C57Bl6/J male mice were chronically implanted with electrodes for EEG and sleep-wake monitoring. Each mouse received 3 doses of GF-015535-00 and zolpidem. Time spent in sleep-wake states and cortical EEG power spectra were analyzed.

RESULTS:

Both zolpidem and GF-015535-00 prominently enhanced slow wave sleep and paradoxical sleep in the mouse. However, as compared with zolpidem, GF-015535-00 showed several important differences: (1) a comparable sleep-enhancing effect was obtained with a 10 fold smaller dose; (2) the induced sleep was less fragmented; (3) the risk of subsequent wake rebound was less prominent; and (4) the cortical EEG power ratio between slow wave sleep and wake was similar to that of natural sleep and thus compatible with physiological sleep.

CONCLUSION:

The characteristics of the sleep-wake effects of GF-015535-00 in mice could be potentially beneficial for its use as a therapeutic compound in the treatment of insomnia. Further investigations are required to assess whether the same characteristics are conserved in other animal models and humans.

• Authors: Christelle Anaclet, Mei Zhang, Chunmei Zhao, Colette Buda, Laurent Seugnet, Jian-Sheng Lin
• Journal: Sleep (Sleep) Vol. 35 Issue 1 Pg. 103-11 (Jan 01 2012) ISSN: 1550-9109 [Electronic] United States
• PMID: 22215924 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gabra1 protein, mouse
• Hypnotics and Sedatives
• Pyridines
• Receptors, GABA-A
• Zolpidem

Topics

• Animals
• Brain (drug effects, physiology)
• Dose-Response Relationship, Drug
• Electroencephalography (drug effects)
• Hypnotics and Sedatives (pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• Pyridines (pharmacology)
• Receptors, GABA-A (drug effects)
• Sleep (drug effects, physiology)
• Sleep Stages (drug effects, physiology)
• Zolpidem