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Mode, speed and duration of action of hypnotics

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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the Z-drugs (zopiclone, zolpidem, zaleplon) are chemically distinct from benzodiazepines - however both classes of drug work in the same way (1)

  • Z-drugs are an excellent substitute to traditional benzodiazepines (2)
  • compared to benzodiazepine there is a lower incidence of amnesia, daytime sleepiness, respiratory depression, orthostatic hypotension and falls (2)

  • hypnotics work via enhancement of neuronal inhibition by gamma-aminobutyric acid (GABA), by binding to specific sites (benzodiazepine receptors) on GABAA receptors in the brain
    • various benzodiazepine receptor subtypes are thought to mediate different functional effects:
      • alpha1 subtypes have been linked to sedative, hypnotic and amnesic effects
      • alpha 1 and alpha 2 to anxiolytic effects
      • benzodiazepines and zopiclone are non-selective agonists at these sites
      • zolpidem and zaleplon are more selective for alpha1 subtypes - however, the clinical relevance of such selectivity is unproven
  • benzodiazepine hypnotics and Z-drugs have a rapid onset of action (between 30 and 90 minutes), but Z-drugs are shorter-acting than any currently licensed benzodiazepine hypnotic
    • benzodiazepines
      • duration of action:
        • loprazolam (elimination half-life 6-12 hours) and lormetazepam (half-life 10-12 hours) have relatively short half-lives
        • lorazepam (half-life 10-20 hours) and temazepam (half-life 8-22 hours) have intermediate half-lives
        • nitrazepam (half-life 15-38 hours) and diazepam and its active metabolites (half-life 20-200 hours) are long-acting benzodiazepines
    • Z-drugs
      • duration of action
        • zopiclone, following a usual adult dose (7.5mg), half-life is 3.5-6 hours
        • zolpidem (10mg), half-life is around 2.5 hours
        • zaleplon is very short-acting: plasma concentration peaks around 1 hour after ingestion (of 10mg), and the elimination half-life is also around 1 hour


  1. 1. Drug and Therapeutics Bulletin (2004); 42(12):89-93.
  2. 2. Budur K et al. Advances in treating insomia. Cleveland Clinic Journal of Medicine 2007;74(4):251-266

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