| | Benzodiazepine-related hypnotics裏Three newer non-benzodiazepine hypnotic agents have been developed and FDA-approved for the treatment of insomnia. Ambien, zaleplon (Sonata), and eszopiclone (Lunesta) are rapid-onset, short duration of action drugs that act on GABAA receptors. Their mechanism of action is not completely understood, but they can be conceptualized as benzodiazepine receptor agonists. This new generation of drugs may offer advantages over benzodiazepines in terms of safety (less tolerance and dependence). They have largely replaced the benzodiazepines as hypnotic medicines of choice, although they lack the anxiolytic, anticonvulsant, and muscle-relaxant properties of the benzodiazepines. All three of these agents impair memory and/or performance of complex tasks in ways that are similar to benzodiazepines. They do not affect stage 4 sleep, as do the benzodiazepines. Zolpidem and zaleplon are reinforcing to alcoholics and drug addicts, underscoring the fact that the abuse potential of these drugs appears to be similar to that of benzodiazepines. Case reports of zolpidema and zaleplon abuse have been noted. Zolpidem has a half-life of about two hours, which is consistent with therapeutic activity over a typical eight hours of sleep. Zaleplon has a one hour half-life that offers the possibility of dosing in the middle of the night for broken sleep. For this reason zaleplon is approved for use both at bedtime and in midsleep periods of insomnia. Eszopiclone has a half-life of five hours, appears to have relatively low abuse potential, and is approved for long-term use.
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