Z-drug

Chemical structure of the prototypical Z-drug zolpidem.

Z-drugs are a group of nonbenzodiazepine drugs with effects similar to benzodiazepines, which are used in the treatment of insomnia, and most of whose names start with the letter "Z". Some Z-drugs may have advantages over benzodiazepines. Benzodiazepines actually worsen sleep architecture, whereas the Z-drug zaleplon (Sonata) may have less or no disruption of sleep architecture.

History

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.

Pharmacology

There are three primary groups of Z-drugs, all of which can be labeled nonbenzodiazepines. Listed below are three distinct groups of CNS sedative-hypnotics:

• Imidazopyridines: zolpidem (Stilnoct, Ambien, Ambien CR, Intermezzo, Stilnox)
• Cyclopyrrolones: zopiclone (Imovane, Zimovane, Imrest), eszopiclone (Lunesta)
• Pyrazolopyrimidines: zaleplon (Sonata, Starnoc, Andante)

All of these groups are believed to modulate benzodiazepine specific subunit sites, as specific agonists of the GABA_A 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 GABA_A receptor.

See also

• Alpidem
• Indiplon
• Nonbenzodiazepine
• Date rape drug