Z-drugs (Non-benzodiazepine Hypnotics)

Z-drugs (Non-benzodiazepine Hypnotics)

1. Definition, scope & nomenclature

• The Z-drugs ("Z compounds") are a class of non-benzodiazepine hypnotics introduced over the past two decades that, despite being structurally unrelated to benzodiazepines (BZDs) and to each other, act as agonists at the benzodiazepine binding site of the GABA_a receptor — their therapeutic efficacy as hypnotics is due to this shared mechanism (G&G 14e Ch.22, p.433).
• The four members all begin with the letter Z — zaleplon, zolpidem, zopiclone, and eszopiclone (the S(+)-enantiomer of zopiclone) (G&G 14e Ch.22, p.433; Stahl Ch.11, p.454).
• A sedative subdues excitement and calms the subject without inducing sleep (some drowsiness may occur); a hypnotic induces and/or maintains sleep resembling normal arousable sleep in its EEG characteristics, from which the recipient can be aroused easily (KDT 8e Ch.29, p.424; G&G 14e Ch.22, p.427).
• Z-drugs are classed clinically among sedative-hypnotics, a grouping defined by clinical use rather than chemical structure (Katzung 16e Ch.22, p.399).
• Stahl reframes the entire BZD/Z-drug/barbiturate family as GABA_a positive allosteric modulators (PAMs) — agents that enhance GABA action by binding to a site different from where GABA itself binds (Stahl Ch.11, pp.454–455).
• Bold first mention: treatment of insomnia is the single most important use of this drug class (KDT 8e Ch.29, p.424).
• Over the last decade the Z compounds have largely replaced benzodiazepines in the treatment of insomnia (G&G 14e Ch.22, p.433; KDT 8e Ch.29, p.432).