Category:Z-Drugs (Non-Benzodiazepine Hypnotics)

The Z-drugs, or non-benzodiazepine hypnotics, are a small class of sleep medicines created in the 1980s with a single purpose: to be the hypnotic that the benzodiazepines, by then sliding into a dependence crisis, could no longer safely be. The first of them came out of the French pharmaceutical industry in the 1980s, zopiclone and then zolpidem, and they were joined later by zaleplon and by eszopiclone. They are not, chemically, a single family, nor are they related to the benzodiazepines; the informal name simply records that three of the four happen to begin with the letter Z. What they share is a target. Like the benzodiazepines, the Z-drugs act at the GABA-A receptor, the receptor for the brain's principal inhibitory neurotransmitter, and at the same site on it.^[1]

The promise lay in selectivity. The GABA-A receptor exists in several subtypes, and the Z-drugs, zolpidem most of all, bind with some preference to the subtype richest in the alpha-1 subunit, the one most associated with sedation rather than with the anti-anxiety, muscle-relaxant, and anticonvulsant effects that the benzodiazepines produce alongside sleep. The hope was a cleaner hypnotic: sleep without the daytime grogginess, the tolerance, and above all the dependence that had overtaken the benzodiazepines.^[1] For a time the Z-drugs were prescribed heavily on that promise, and they remain among the most commonly used sleep medicines.

The promise held only in part. Like the benzodiazepines they were meant to improve upon, the Z-drugs can produce tolerance and dependence, with a withdrawal syndrome on stopping; in older adults they are associated with falls and with fractures.^[2] They can leave a next-day impairment that the person does not notice, and they carry a hazard of their own: complex sleep behaviors, in which a person walks, eats, or even drives while not fully awake and has no memory of it afterward. In 2019, after reports of serious injuries and deaths, United States regulators placed a boxed warning, their strongest, on zolpidem, zaleplon, and eszopiclone for these behaviors.^[3]

Current guidance treats the Z-drugs with the same caution it brings to the benzodiazepines: short courses, the lowest effective dose, particular care in older adults, and a preference, where it can be arranged, for cognitive behavioral therapy for insomnia over any sleep medicine at all.^[4] The class that was meant to be the safe answer to the benzodiazepines turned out to be, in most of the ways that matter, their near-equivalent. This category collects the wiki's pages for the four Z-drugs.

The class has four members, drawn from three unrelated chemical families, all of them acting at the benzodiazepine site of the GABA-A receptor.

• zopiclone: a cyclopyrrolone, the first of the Z-drugs to reach use; widely prescribed outside the United States.
• zolpidem: an imidazopyridine, the most widely used of the four, sold as Ambien and under many other names.
• zaleplon: a pyrazolopyrimidine, the shortest-acting of the class, suited to difficulty falling asleep rather than staying asleep.
• eszopiclone: the active enantiomer of zopiclone, developed and marketed as a single-isomer medicine in its own right.

This category indexes the four Z-drugs, the non-benzodiazepine hypnotics that act at the benzodiazepine site of the GABA-A receptor. The boundary is narrow and well defined: the class has only these four members.

The Z-drugs sit close to the benzodiazepines, with which they share a receptor site and most of their hazards, and to the wider group of sedative and hypnotic medicines. A medicine is indexed here only if it is one of the four Z-drugs themselves; other modern sleep medicines that work by different routes, among them the melatonin-receptor agonists and the orexin-receptor antagonists, are indexed under their own categories.

Each Z-drug indexed here has its own page, built on the wiki's standard structure for a medicine: a history-first account, then pharmacology, indications, adverse effects, and interactions.

This is one of the wiki's MedCategory class-overview pages. It carries the MedCategory and MedCategoryFull marker tags; the second suppresses the member list that MediaWiki would otherwise generate automatically, leaving the curated index above as the only one the reader sees. The category sits beneath Medicines and beneath Pharmaceutical, the origin category for medicines that came into use through scientific discovery rather than traditional practice.