Clinical evaluation of zaleplon in the treatment of insomnia

Abstract

Zaleplon is a pyrazolopyrimidine hypnotic used for the treatment of insomnia. Zaleplon binds preferentially at the α1β2γ2 subunit of gamma aminobutyric acid type A (GABAA) receptors in the central nervous system, and has a half-life of about one hour. Efficacy studies show that zaleplon is a suitable hypnotic for sleep initiation purposes. However, because of its short half-life, zaleplon is less effective in sleep maintenance when compared with other hypnotics. Nevertheless, zaleplon does increase total sleep time. No rebound effects are observed after treatment discontinuation. The use of zaleplon is relatively safe. Adverse effects are mild and of short duration. No important interactions have been reported, and there is no evidence of abuse potential. Relative to benzodiazepine hypnotics, the biggest advantage of zaleplon is that current evidence suggests it does not produce residual next-day effects. As early as four hours after intake of zaleplon, no effects on cognitive, memory, psychomotor performance, and the ability to drive a car have been reported. Future studies should confirm these findings, and comparisons with new nonbenzodiazepine hypnotics should determine the importance of zaleplon in the future treatment of insomnia.

Keywords: efficacy; hypnotics; residual effects; safety; zaleplon; zolpidem.

Figure 1

Chemical structure of zaleplon (N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7 yl)phenyl)]-N-ethylacetamide.

Figure 2

Mean (standard deviation) time to sleep onset (left panel), mean (standard deviation) number of awakenings (middle panel), and mean total time slept (right panel) in elderly patients using zaleplon nightly for 6–12 months. Copyright © 2005. World Association of Sleep Medicine. All rights reserved. Adapted with permission from Ancoli-Israel S, Richardson GS, Mangano RM, Jenkins L, Hall P, Jones WS. Long term use of sedative hypnotics in older patients with insomnia. Sleep Med. 2005;6(2):107–13.

Figure 3

Number of correct responses in a serial reaction time task after ingestion of placebo, time-released melatonin 6 mg, zaleplon 10 mg, zopiclone 7.5 mg, and temazepam 15 mg. Higher number of responses represents better performance. Data are mean values (± standard error of mean) of 23 subjects. Copyright © 2003. World Association of Sleep Medicine. All rights reserved. Adapted with permission from Paul MA, Gray G, Kenny G, Pigeau RA. Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. Aviat Space Environ Med. 2003;74(12):1263–70.