Zaleplon

Zaleplon is a nonbenzodiazepine hypnotic in the pyrazolopyrimidine class, marketed as a Z-drug. It acts as a positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site, with relative selectivity for the alpha-1 subunit. This profile yields sedative effects with minimal anxiolytic, anticonvulsant, or muscle-relaxant activity, and it is used for the short-term treatment of insomnia, particularly sleep-onset difficulties.

Pharmacokinetics: Zaleplon is rapidly absorbed, with onset of sleep-promoting effects typically within 15–30 minutes. It has a very short plasma half-life of about 1 hour, resulting in minimal next-day sedation for many patients. It is primarily metabolized in the liver by aldehyde oxidase to inactive metabolites and excreted in urine and feces; cytochrome P450 involvement is limited, contributing to relatively few drug interactions compared with some other sedative-hypnotics.

Administration: The usual dose for adults is 5–10 mg taken immediately before bedtime; the maximum recommended daily dose is 20 mg. Lower starting doses are used for the elderly or individuals with hepatic impairment. Zaleplon’s short duration makes it suitable for sleep onset but not for maintenance of sleep.

Safety and adverse effects: Common adverse effects include dizziness, headache, and somnolence. Rare but important events include complex sleep-related behaviors (for example, sleep-driving) and anterograde amnesia. Caution is advised when driving or operating machinery, with concurrent alcohol use, or in patients with hepatic impairment, respiratory disorders, or a history of substance use.

Regulatory status: Zaleplon was approved for insomnia in the late 1990s and is available under the brand name Sonata and in generic form in many countries. It is generally recommended for short-term use due to risks of dependence and withdrawal with prolonged use.