Zaleplon (N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl) phenyl]-N-ethyl
acetamide) is a non-
benzodiazepine recently introduced for clinical use. This agent is indicated for the short-term treatment of
insomnia. Preclinical studies have shown that the
benzodiazepines triazolam and Ro17-1812 can substitute for
zaleplon in animals trained to distinguish
zaleplon from saline. The
benzodiazepine antagonist
flumazenil can antagonise the discriminative stimulus effect of
zaleplon. These findings suggest that
zaleplon is recognised by animals as a
benzodiazepine agent.
Zaleplon is active after ip. and
oral administration in a variety of motor performance tests, including locomotor activity, rotarod and the loaded grid.
Zaleplon has been shown to be active in a number of different
anticonvulsant models, including the
pentylenetetrazole,
isoniazid and electroshock models. The compound is also reported to be active against convulsions induced by
bicuculline,
picrotoxin and
strychnine. Studies in
anxiolytic models suggest that
zaleplon may have weak
anxiolytic activity. From preclinical studies, it appears
zaleplon possesses a reduced risk of tolerance compared to
triazolam, is less likely to potentiate the effects of
ethanol and is unlikely to produce amnestic effects. In man,
zaleplon is rapidly absorbed and undergoes extensive presystemic metabolism. The compound has a plasma half-life of approximately one hour and is metabolised primarily via the
aldehyde oxidase system to form 5-oxo-zaleplon. This metabolite, along with other minor metabolites formed in vivo, do not appear to contribute to the activity of
zaleplon. Metabolites of
zaleplon are excreted primarily via the urine. Phase I studies suggest that single daytime doses of
zaleplon up to 15 mg are well-tolerated. Short-term impairment of performance occurs when
zaleplon is administered during the day at doses epsilon 20 mg. However, given the short half-life of the compound, significant impairment of daytime performance is unlikely if
zaleplon is administered at bedtime or shortly after retiring for the evening. Results from Phase II/III studies suggest that
zaleplon (5 - 20 mg) produces a dose-dependent reduction in sleep latency in patients suffering from
primary insomnia. The clinical efficacy of
zaleplon persists for at least four weeks at doses of 10 mg and 20 mg. Studies in patients with a history of
drug abuse suggest that the abuse potential of
zaleplon (at doses above the therapeutic dose range) is similar to that seen with the
benzodiazepine triazolam.