indication

For the treatment of short-term treatment of insomnia in adults.

pharmacology

Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABA_BZ) receptor complex. Subunit modulation of the GABA_BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zaleplon also binds selectively to the CNS GABA_A-receptor chloride ionophore complex at benzodiazepine(BZ) omega-1 (BZ1, ο1) receptors.

mechanism of action

Zaleplon exerts its action through subunit modulation of the GABA_BZ receptor chloride channel macromolecular complex. Zaleplon also binds selectively to the brain omega-1 receptor located on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.

toxicity

Side effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness

biotransformation

Zaleplon is primarily metabolized by aldehyde oxidase.

absorption

Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.

half life

Approximately 1 hour

route of elimination

Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. After oral administration, zaleplon is extensively metabolized, with less than 1% of the dose excreted unchanged in urine. Renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose.

drug interactions

Cimetidine: Cimetidine may increase the serum concentration of zaleplon by decreasing its metabolism. Reduce the initial dose of zaleplon to 5 mg in patients receiving cimetidine.

Methotrimeprazine: Additive CNS depressant effects may occur. A dose reduction of zaleplon may be required. Monitor for increased CNS depression during concomitant therapy.

Rifampin: Rifampin decreases the effect of zaleplon

Triprolidine: The CNS depressants, Triprolidine and Zaleplon, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.