Sedative-hypnotic agents nonbenzodiazepines

The newer sedative-hypnotics that are not benzodiazepines are rapidly becoming the first-line treatment for insomnia. These agents not only have pharmacodynamic advantages over benzodiazepines in terms of their mechanism of action, but perhaps more importantly, pharmacokinetic advantages as well. Three nonbenzodiazepine sedative-hypnotic agents that are now available are zaleplon (a pyrazolopyrimidine), zopiclone (a cyclopyrrolone not available in the United States), and zolpidem (an imidazopyridine) (Figs. 8—28-8—30 Table 8—4). 

The nonbenzodiazepine sedative-hypnotics zaleplon, zolpidem, and zopiclone are replacing benzodiazepine sedative-hypnotics as first-line treatments for insomnia. Some antidepressants, such as sedating tricyclic antidepressants and trazodone, are also used as sedative-hypnotic agents for the treatment of insomnia. 

Zolpidem (Fig. 8—29). This was the first omega 1 selective nonbenzodiazepine sedative-hypnotic and rapidly replaced benzodiazepines as the preferred agent for many patients and prescribers. It has a somewhat later peak drug concentration (2 to 3 hours) and longer half-life (1.5 to 3 hours) than zaleplon. 

Nonbenzodiazepine ligands at benzodiazepine sites This is a variation on the theme of partial benzodiazepine agonists, as these agents act at the same or similar site as benzodiazepines but are not structurally related to them. Thus, the pharmacology of nonbenzodiazepines is that of a partial agonist, but their chemistry is different from that of a benzodiazepine. This is similar to the approach that novel sedative-hypnotics such as zaleplon and zolpidem have taken, and perhaps a less sedating nonbenzodiazepine partial agonist could hold promise for the treatment of panic disorder. 

Sedative-hypnotics fall into two general categories benzodiazepines and nonbenzodiazepines (Table 6-1). At present, benzodiazepines are typically used to promote normal sedation and sleep, especially in relatively acute or short-term situations. These agents will be addressed first, followed by a description of the nonbenzodiazepine hypnotics. 

Nonbenzodiazepine sedative-hypnotics. The non-BZD hypnotic zolpidem (Ambien) is a newer sleeping agent that is thought to work on more specific subdivisions of the GABA receptor complex than, for example, some of the older benzodiazepine agents. It is indicated for short-term insomnia and is generally limited to seven to 10 days of use. 

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