Hypnotic — gaboxadol
Long-term sleep deprivation can lead to a variety of health problems. Some 20-35% of adults in industrialised countries are estimated to suffer from difficulty in sleeping. Drugs have been used to induce sleep for years, with the pharmaceutical industry's first contribution being chloral hydrate in the 1860s, but many more effective modern hypnotics are available. However, they are often associated with side-effects and dependency problems, and several medicines, such as zopiclone and zolpidem are now available which avoid many of the side-effects seen with benzodiazepines.
Hypnotics act at GABA receptors, and the newer medicines circumvent many of these side-effects by being specific for one of the different sub-types, unlike benzodiazepines. A new hypnotic under development is the GABAA agonist gaboxadol. It has been licensed by Lundbeck from the Max Planck Institute, and was previously referred to as LU 02-030.
Sleep disorders are a particular problem in the elderly. In a double blind, placebo-controlled study in 10 healthy elderly women, the subjects were given 15mg of gaboxadol or placebo.1 Gaboxadol did not affect endocrine activity, but significantly reduced perceived sleep latency, elevated self-estimated total sleep time, and increased sleep efficiency by decreasing intermittent wakefulness. It also powerfully augmented low-frequency activity in the EEG within non-REM sleep.
A further study in young, healthy subjects looked at the drug's effect on disturbed night-time sleep in subjects who had taken a late afternoon nap. Compared with placebo, a single oral dose of 20mg led to a post-nap night having a shorter sleep latency, significantly decreased intermittent wakefulness, and increased total sleep time, as well as increasing subjective sleep quality.2 The drug appears to counteract a nap's disruption of subsequent sleep and may help subjects to fall asleep, as well as promoting deep sleep and sleep maintenance.
Gaboxadol is currently in Phase II/III trials as a treatment for sleep disorders. Because it does not impair sleep quality, and may be suitable for long-term treatment without producing either tolerance or withdrawal symptoms, it may prove a useful treatment option for sleeping problems.