Zaleplon
Z-drug hypnotics
Z-drug hypnotics
An ultra-short-acting Z-drug that shortens the time to fall asleep without adding total sleep. It can cause complex sleep behaviours such as sleep-driving.
Quick facts
- Group
- Z-drug hypnotics
- Target
- GABA-A receptor (α1-containing), benzodiazepine site
- Used for
- Short-term treatment of insomnia
- Key effects
- Headache and dizziness · Somnolence · Nausea
- Monitor
- Sleep onset and next-day alertness
- ATC
- N05CF03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows zolpidem, another Z-drug, in the human GABA-A receptor; zaleplon acts at the same benzodiazepine site.
Zaleplon is a non-benzodiazepine (a pyrazolopyrimidine) that binds the benzodiazepine site of GABA-A receptors containing the α1 subunit (the omega-1 site). It strengthens GABA's chloride current. Its very short action shortens sleep onset but does not lengthen total sleep.
- Binds α1-containing GABA-A receptors (omega-1 site)
- GABA's chloride current grows stronger
- Sleep comes sooner; the effect ends within hours
Indications
- Short-term treatment of insomnia with difficulty falling asleep Insomnia disorder →
Adverse effects
Common
- Headache and dizziness
- Somnolence
- Nausea
- Amnesia and tingling
Contraindications
- Hypersensitivity to zaleplon
Key interactions
- Alcohol and other CNS depressants
- Additive sedation and impairment
- Cimetidine
- Higher zaleplon levels; lower starting dose
- Rifampin (strong CYP3A4 inducer)
- Much lower zaleplon levels
What is monitored
- Sleep onset and next-day alertness
- Unusual night-time behaviour and mood
Administration and safety
- Given by mouth right before bedtime, or after getting into bed and failing to fall asleep
- Not with or right after a heavy, high-fat meal
- Controlled medicine (Schedule IV in the United States)
Pregnancy and breastfeeding
There are no studies in pregnant women and its use is not recommended; it is avoided during breastfeeding.
Nursing care
- Check that a full night in bed is possible before giving it
- Ask about alcohol and other sedatives
- Teach to report sleep-driving or other actions done while not fully awake
- Reassess if insomnia persists after 7 to 10 days
Pharmacokinetics
- Absorption
- About 30% bioavailable; a heavy high-fat meal delays it and lowers the peak
- Metabolism
- Mainly by aldehyde oxidase, with a smaller CYP3A4 role
- Half-life
- About 1 hour
Test yourself
Think of the answer, then tap the question to see it.
Why does zaleplon not increase total sleep time?
Its half-life is about one hour, so it only helps with falling asleep.
Which enzyme mainly metabolises zaleplon?
Aldehyde oxidase (CYP3A4 has a smaller role).
Which GABA-A subunit site does it prefer?
The α1 (omega-1) benzodiazepine site.
Connections
← Back to the class: Z-drug hypnotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ZALEPLON capsule (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.