Effect of Repeated Gaboxadol Administration on Night Sleep and Next-Day Performance in Healthy Elderly Subjects

Abstract

Aging is associated with dramatic reductions in sleep continuity and sleep intensity. Since gaboxadol, a selective GABA A receptor agonist, has been demonstrated to improve sleep consolidation and promote deep sleep, it may be an effective hypnotic, particularly for elderly patients with insomnia. In the present study, we investigated the effects of subchronic gaboxadol administration on nocturnal sleep and its residual effects during the next days in elderly subjects. This was a randomized, double-blind, placebo-controlled, balanced crossover study in 10 healthy elderly subjects without sleep complaints. The subjects were administered either placebo or 15 mg gaboxadol hydrochloride at bedtime on three consecutive nights. Sleep was recorded during each night from 2300 to 0700 h and tests assessing attention (target detection, stroop test) and memory function (visual form recognition, immediate word recall, digit span) were applied at 0900, 1400, and 1700 h during the following days. Compared with placebo, gaboxadol significantly shortened subjective sleep onset latency and increased self-rated sleep intensity and quality. Polysomnographic recordings showed that it significantly decreased the number of awakenings, the amount of intermittent wakefulness, and stage 1, and increased slow wave sleep and stage 2. These effects were stable over the three nights. None of the subjects reported side effects. Next-day cognitive performance was not affected by gaboxadol. Gaboxadol persistently improved subjective and objective sleep quality and was devoid of residual effects. Thus, at the employed dose, it seems an effective hypnotic in elderly subjects.

Eszopiclone

“…Gaboxadol increases the proportion of non-REM (rapid eye movement) sleep, specifically slow-wave sleep (deep sleep), without affecting REM sleep. 30 Indiplon, another GABA A receptor agonist being investigated for the treatment of insomnia, has been shown to have selective binding for the α-1 site of the GABA A receptor, which is thought to minimize the adverse effects associated with benzodiazepines. 31 Ramelteon, a melatonin receptor agonist, is being studied for the treatment of sleep disorders.…”

GABA A receptor α4 subunits mediate extrasynaptic inhibition in thalamus and dentate gyrus and the action of gaboxadol

“…GBX is known to shorten the latency to sleep and to enhance the quality of sleep in man (33,34) and to produce sedation, the loss of motor coordination, and the loss of righting reflex in The open-field assay was used to measure the sedative effect of 10 mg͞kg GBX (n ϭ 7-10 mice per genotype per treatment). Total locomotor activity after injection with saline (SAL) or GBX is displayed.…”

Treatment of sleep disorders in elderly patients

“…Assistive devices Insomnia • New promising pharmacologic therapies under development include drugs such as GABA-A receptor agonists, indiplon [108] and gaboxadol [109], which seem to improve objective and subjective sleep quality in elderly patients, and the novel melatonin receptor agonist, ramelteon [110].…”