Nonbenzodiazepine hypnotic drugs

Sanger DJ. The pharmacology and mechanisms of action of new generation, nonbenzodiazepine hypnotic agents. CNS Drugs 2004 18(Supplement 1) 9-15, 41-45. 

Pharmacology Zolpidem is a nonbenzodiazepine hypnotic. While zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with a GABA-BZ receptor complex and shares some of the pharmacological properties of the benzodiazepines. 

Pharmacoiogy Zaleplon is a nonbenzodiazepine hypnotic. Zaleplon has a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties. 

To review the drug treatments for insomnia, including newer nonbenzodiazepine hypnotics as well as benzodiazepine and other hypnotics. 

Related hypnotics that also act at benzodiazepine receptors are the newer agents zolpidem, a imida-zopyridine, zaleplon a pyrazolopyrimidine and the cyclopyrrolone zopiclone. Zopiclone might have a role for the treatment of benzodiazepine addiction. In patients in whom zopiclone was substituted for a benzodiazepine for 1 month and then itself abmptly terminated, improved sleep was reported during the zopiclone treatment, and withdrawal effects were absent on discontinuation of zopiclone. A series of non-sedating anxiolytic drugs derived from the same structural families as the above mentioned nonbenzodiazepines, have been developed, such as alpi-dem and pagoclone. 

The fundamental neurobiological importance of the GABA A receptor is underscored by observations that even more receptor sites exist at or near this complex (Fig. 8—20). This includes receptor sites for nonbenzodiazepine sedative-hypnotics such as zolpidem and zaleplon, for the convulsant drug picrotoxin, for the anticonvulsant barbiturates, and perhaps even for alcohol. This receptor complex is hypothetically responsible in part for mediating such wide-ranging CNS activities as seizures, anticonvulsant drug effects, and the behavioral effects of alcohol, as well as the known anxiolytic, sedative-hypnotic, and muscle relaxant effects of the benzodiazepines. 

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. 

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