![]() ![]() At the primary efficacy endpoint (nights 29 and 30) in a 35-night sleep laboratory study, polysomnographic recordings showed that wakefulness was not significantly longer with Sonata than with placebo during the last quarter of the night. Zaleplon has a short half-life and no active metabolites. This sequence of events is believed to be responsible for two clinical findings reported to occur after several weeks of nightly use of other rapidly eliminated hypnotics: increased wakefulness during the last quarter of the night and the appearance of increased signs of daytime anxiety. If the drug has a short elimination half-life, it is possible that a relative deficiency of the drug or its active metabolites (i.e., in relationship to the receptor site) may occur at some point in the interval between each night's use. In a 35‑night study, Sonata 10 mg was significantly more effective than placebo in reducing LPS at the primary efficacy endpoint on nights 29 and 30.ĭuring nightly use for an extended period, pharmacodynamic tolerance or adaptation to some effects of hypnotics may develop. At later time points in 5-, 14-, and 28-night studies, a reduction in LPS from baseline was observed for all treatment groups, including the placebo group, and thus, a significant difference between Sonata and placebo was not seen beyond 2 nights. Overall, these studies demonstrated a superiority of Sonata 10 mg and 20 mg over placebo in reducing LPS on the first 2 nights of treatment. Sleep latency with Sonata 10 mg and 20 mg was on the order of 10–20 minutes (15%–30%) less than with placebo in these studies.Īdult outpatients with chronic insomnia were evaluated in six double-blind, parallel-group sleep laboratory studies that varied in duration from a single night up to 35 nights. The 5-mg dose was less consistently effective than were the 10-mg and 20‑mg doses. Although both doses were effective, the effect was greater and more consistent for the 20-mg dose. Sonata 10 mg and 20 mg were consistently superior to placebo for TSO, generally for the full duration of all three studies. ![]() Studies of binding of zaleplon to recombinant GABA A receptors (α 1β 1γ 2 and α 2β 1γ 2 ) have shown that zaleplon has a low affinity for these receptors, with preferential binding to the omega-1 receptor.Īdult outpatients with chronic insomnia were evaluated in three double-blind, parallel-group outpatient studies, one of 2 weeks duration and two of 4 weeks duration, that compared the effects of Sonata at doses of 5 mg (in two studies), 10 mg, and 20 mg with placebo on a subjective measure of time to sleep onset (TSO). ![]() ![]() Other nonclinical studies have also shown that zaleplon binds selectively to the brain omega-1 receptor situated on the alpha subunit of the GABA A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding. Subunit modulation of the GABA-BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. While Sonata (zaleplon) is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma‑aminobutyric acid-benzodiazepine (GABA-BZ) receptor complex. ![]()
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