Zdrugs

Zdrugs, or Z-drugs, refer to a class of non-benzodiazepine hypnotics used to treat insomnia. The main agents are zolpidem, zaleplon, and eszopiclone. They act as positive allosteric modulators at the GABA-A receptor benzodiazepine site, with relatively greater selectivity for subtypes associated with sedation, particularly those involving the alpha-1 subunit. This pharmacology is intended to promote sleep with a lower profile of muscle relaxation and anxiolytic effects than traditional benzodiazepines.

Clinically, Z-drugs are prescribed for short-term treatment of insomnia in adults, typically when there is trouble falling asleep or staying asleep. Guidelines generally recommend limiting use to two to four weeks due to risks of tolerance, dependence, and withdrawal. They are not considered first-line treatments for chronic insomnia.

Pharmacokinetics vary among the compounds. Zolpidem has rapid onset, usually within 15–30 minutes, and a short half-life of about 2–3 hours. Zaleplon also acts quickly with an even shorter duration, around one hour. Eszopiclone has a longer duration of action and a half-life near six hours, which can influence next-day effects. Metabolism involves hepatic enzymes, and interactions with other central nervous system depressants can alter effects.

Adverse effects commonly include daytime drowsiness, dizziness, and headaches. They can cause anterograde amnesia and, in some cases, complex sleep-related behaviors such as sleepwalking or sleep-eating. Caution is advised with alcohol or other depressants, and there is heightened risk for older adults, including falls or confusion. Dependence, tolerance, and withdrawal can occur with prolonged use.

Regulatory status typically designates Z-drugs as prescription-only medications, often with controlled-substance scheduling in various jurisdictions.