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Chemical structure of the prototypical Z-drug zolpidem.

Z-drugs are a group of nonbenzodiazepine drugs with effects similar to benzodiazepines. These drugs (the names of which usually begin with the letter "Z") are used in the treatment of sleep problems.[1]

Medical uses[edit]

They are used to treat insomnia.[2]

Adverse effects[edit]

Sleeping pills, including the z-drugs, have been associated with an increased risk of death.[3]

In older people this family of medications increases the risk of fractures and falls.[2]

The Z-drug zaleplon may have fewer side effects compared to benzodiazepines.[4]


There are three primary groups of Z-drugs:

They are categorized as nonbenzodiazepines. All of these groups are believed to modulate benzodiazepine specific subunit sites, as specific agonists of the GABAA receptors. It is thought that the primary mode of action utilized by Z-drugs is selective, and carries a high affinity for the a1 hypnotic-inducing site on the benzodiazepine subunit within the GABAA receptor.


Z-drugs emerged in the last years of the 1980s and early 1990s, with zopiclone (Imovane) approved by the British National Health Service as early as 1989, quickly followed by Sanofi with zolpidem (Ambien). By 1999, King Pharmaceuticals had finalized approval with the American Food and Drug Administration (FDA) to market zaleplon (Sonata, Starnoc) across the US. In 2005, the FDA approved eszopiclone (Lunesta) the (S)-enantiomer of zopiclone; that same year, 2005, the FDA finalized approval for Ambien CR, or extended-release zolpidem. Most recently, in 2012 the FDA approved Intermezzo, which still utilizes zolpidem as its active ingredient, but is marketed for middle-of-the-night insomnia, available in doses only half of the strength of immediate-release Ambien to avoid residual next-day sedation.

See also[edit]


  1. ^ "What's wrong with prescribing hypnotics?". Drug Ther Bull. 42 (12): 89–93. December 2004. doi:10.1136/dtb.2004.421289. PMID 15587763.
  2. ^ a b Treves, N; Perlman, A; Kolenberg Geron, L; Asaly, A; Matok, I (1 March 2018). "Z-drugs and risk for falls and fractures in older adults-a systematic review and meta-analysis". Age and Ageing. 47 (2): 201–208. doi:10.1093/ageing/afx167. PMID 29077902.
  3. ^ Kripke, DF (February 2016). "Mortality Risk of Hypnotics: Strengths and Limits of Evidence" (PDF). Drug Safety. 39 (2): 93–107. doi:10.1007/s40264-015-0362-0. PMID 26563222.
  4. ^ Barbera J, Shapiro C (2005). "Benefit-risk assessment of zaleplon in the treatment of insomnia". Drug Saf. 28 (4): 301–18. doi:10.2165/00002018-200528040-00003. PMID 15783240.