zolpidem, sedative-hypnotic drug used in the treatment of insomnia. Zolpidem decreases the excitability of neurons in the central nervous system, which has a calming effect on the brain that helps patients fall asleep and remain asleep through the night. Zolpidem was first synthesized in the early 1980s by researchers at the French pharmaceutical company Synthélabo Recherche. The drug was approved by the U.S. Food and Drug Administration (FDA) in 1992 under the trade name Ambien. The drug subsequently acquired other trade names, among them Edluar, Intermezzo, and Zolpimist, and in 2007 it became available in a generic formulation.
Zolpidem is classified as an imidazopyridine drug, owing to its cyclic nitrogen-containing structure, and is sometimes also referred to as a Z-drug, or a nonbenzodiazepine drug, because, while structurally different from the group of sedative-hypnotic drugs known as benzodiazepines, its sedative effects are similar. Indeed, zolpidem exerts its effects by binding to and modulating the activity of gamma-aminobutyric acid type A (GABAA) receptors that contain a BZ site, so named because it is the binding site for benzodiazepine drugs. GABAA receptors, when activated, dampen neuronal signaling and excitability. When this effect is distributed across many neurons, sedation occurs. Thus, binding of zolpidem to the BZ site, by enhancing the inhibitory activity of GABAA receptors, suppresses neural transmission in the brain and induces sleep.
Zolpidem is taken orally, in the form of a capsule, tablet, or spray, and is available in immediate-release (fast-acting) and extended-release (long-acting) formulations. It is typically taken at bedtime to help patients fall asleep, but it may be taken in the middle of the night by persons who have trouble falling back asleep after waking in the night. The drug is usually taken for a period of four to six weeks. Its long-term use increases the risk of chemical dependency, wherein patients show signs of compulsive use and tolerance (requiring increasing doses to achieve the desired effect) and experience withdrawal symptoms, such as agitation, anxiety, or restlessness, when not taking the medication.
Zolpidem has generally mild side effects, including chest pain, confusion, daytime sleepiness, dizziness, fatigue, headache, irritability, and loss of appetite. More-severe side effects may include amnesia, hallucinations, and respiratory infection. In rare instances, the drug may induce phenomena known as complex sleep behaviors, in which individuals are not fully awake but engage in activities normally associated with being awake, such as sleep driving and sleepwalking. Zolpidem interacts with a number of other drugs, particularly alcohol, antidepressants, benzodiazepines, and opioids. When combined with any of these substances, zolpidem use is associated with significantly heightened risk of a wide range of conditions and adverse events, such as depression, hallucinations, respiratory depression, suicidal ideation, and death.