[3] Zaleplon is slightly effective in treating insomnia,[11] primarily characterized by difficulty falling asleep.

Clinicians should devote more attention when prescribing for patients with a history of alcohol or drug abuse, psychotic illness, or depression.

[23] Some evidence suggests zaleplon is not as chemically reinforcing and exhibits far fewer rebound effects when compared with other nonbenzodiazepines, or Z-drugs.

[25] Zaleplon is a high-selectivity,[26] high-affinity ligand of positive modulatory benzodiazepine sites on GABAA receptors.

[30] A meta-analysis of randomized, controlled clinical trials which compared benzodiazepines against zaleplon or other Z-drugs such as zolpidem, zopiclone, and eszopiclone has found few clear and consistent differences between zaleplon and the benzodiazepines in terms of sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia, and daytime alertness.

[32][33] In contrast to non-selective benzodiazepine drugs and zopiclone, zaleplon does not increase power in the β-frequency band.

[34] The ultrashort 1hr half-life gives Zaleplon a unique advantage over other hypnotics because of its lack of next-day residual effects on driving and other performance-related skills.

The first step in the condensation with 3-amino-4-cyanopyrazole can be visualized as involving an addition-elimination reaction sequence on the eneamide function to give a transient intermediate such as 5.

[47] The United States Air Force uses zaleplon as one of the hypnotics approved as a "no-go pill" to help aviators and special-duty personnel sleep in support of mission readiness (with a four-hour restriction on subsequent flight operation).

"Ground tests" are required prior to authorization being issued to use the medication in an operational situation.