Z-drugs (Non-benzodiazepine Hypnotics)

Introduction & nomenclature

• Definition — the Z-drugs ("Z compounds") are a class of non-benzodiazepine hypnotics that, although structurally unrelated to benzodiazepines (BZDs) and to each other, act as agonists at the benzodiazepine binding site of the GABA_a receptor — they share the BZD mechanism but differ in receptor-subtype selectivity.
• The four members — all begin with the letter Z — zaleplon, zolpidem, zopiclone, and eszopiclone (the active S(+)-enantiomer of zopiclone).
• Sedative vs hypnotic — a sedative calms/subdues excitement without inducing sleep; a hypnotic induces and maintains sleep resembling natural arousable sleep on EEG — treatment of insomnia is the single most important use of this class.
• Clinical significance — over the last two decades the Z compounds have largely replaced benzodiazepines as first-line GABA_a-acting hypnotics for insomnia, owing to a higher therapeutic index, smaller effect on sleep architecture and (initially claimed) lower abuse potential.