Other Benzodiazepine Receptor Agonists

OTHER BENZODIAZEPINE RECEPTOR AGONISTS

Zolpidem (Ambien) and zaleplon (Sonata) are struc-turally unrelated to the benzodiazepines, but both drugs share pharmacological properties with the benzodi-azepines. They bind to benzodiazepine receptors and fa-cilitate GABA-mediated inhibition.

In usual sedative doses, zolpidem preserves deep sleep (stages 3 and 4) and has only minor and inconsis-tent effects on REM sleep. Compared with the benzo-diazepines, zolpidem has relatively weak anxiolytic, an-ticonvulsant, and skeletal muscle relaxant properties at therapeutic doses. Zolpidem has a rapid onset and a rel-atively short duration of action. It is well absorbed after oral administration, with approximately 70% bioavail-ability. It undergoes hydroxylation and oxidation to in-active metabolites in the liver. Its elimination half-life is approximately 2.5 hours, which is usually sufficient to provide for a normal 8 hours of sleep without daytime grogginess.

Principal side effects are gastrointestinal and cen-tral nervous system symptoms, including drowsiness, dizziness, and diarrhea. Zolpidem may increase the de-pressant effects of other sedative drugs, such as the an-tipsychotics, tricyclic antidepressants, and antihista-mines.

There is less therapeutic experience with the newer zaleplon than with zolpidem. Zaleplon has a rapid onset and a half-life of approximately 1 hour. It is extensively metabolized by aldehyde dehydrogenase, so that less than 1% of a dose is excreted unchanged. Because of its rapid onset of action and short biological half-life, zale-plon is well suited for treatment of sleep onset insom-nia. Its short half-life often does not ensure a full 8 hours of sleep.