|Systematic (IUPAC) name|
|N-(3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N- ethylacetamide|
|Trade names||Sonata, Starnoc|
|Pregnancy cat.||C (US)|
|Legal status||Schedule IV (US)|
|Routes||Oral (medical), intranasal (recreational)|
| (what is this?)
Zaleplon (marketed under the brand names Sonata and Starnoc) is a sedative/hypnotic, almost entirely used for the management/treatment of insomnia. It is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class.
Sonata (US) is manufactured by King Pharmaceuticals of Bristol, TN; Starnoc has been discontinued in Canada. It's prescribed rarely in the United Kingdom; with zopiclone Imovane being the preferred "Z-Drug" by the National Health Service (NHS), as zaleplon has been discontinued by the NHS.
Medical uses 
Zaleplon is effective in the management/treatment of insomnia, primarily characterized by difficulty falling asleep. Due to its ultra-short elimination half-life, zaleplon may not be effective in premature awakenings.
It may result in an impaired ability to drive the next day, though it has proven promising when compared to other sedative hypnotics and next day residual sedation. It may have advantages over benzodiazepines with less adverse effects.
Never combine zaleplon, or any non-benzodiazepine with any alcoholic beverage as both substances modulate GABAA receptor sites, and in a synergistic manner increase the chances of fatal respiratory depression and asphyxiation from vomiting.
Special populations 
Zaleplon is not recommended for chronic use in the elderly. The elderly are more sensitive to the adverse effects of zaleplon such as cognitive side effects. Zaleplon may increase the risk of injury among the elderly. It should not be used while in pregnancy or lactation, and in patients with a history of alcohol or drug abuse, psychotic illness or depression, clinicians should devote more attention.
When compared with benzodiazepines, nonbenzodiazepines (including zaleplon) appear to offer few significant advantages in efficacy or tolerability among elderly individuals. Long-term use of sedative-hypnotics for insomnia has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment, anterograde amnesia, daytime sedation, musculo-skeletal impairment, and subsequently an increased risk of harm to oneself (e.g. falling) and to others (e.g. automotive accidents). Though, quite obviously as the body and brain age, these aforementioned phenomena are expected events, as they occur daily regardless of ingestion of a sedative-hypnotic. Thus, statistically significant and empirical evidence are arguably still absent as dramatic precautions and conclusions are drawn irrespective of the debilitating realities that accompany insomnia and the fact that these medicines do indeed provide assistance to millions of elderly individuals. It is important to distinguish between the extrapolation of potential side effects relative to the vast number of examples, wherein the sedative-hypnotic has proven therapeutically beneficial and appropriate.
In addition, some contend the efficacy and safety of long-term use of these agents remains to be enumerated, but there is nothing concrete to suggest that long term use poses any direct harm to a person.
Adverse effects 
The side effects of zaleplon are similar to the side effects of benzodiazepines, although with less next-day sedation, and in two studies zaleplon use was found to not cause an increase in road traffic accidents, as compared to other hypnotics currently on the market.
Zaleplon may prompt day-time or next-day residual sedation.
Available data cannot provide a reliable estimate of the incidence of dependence during treatment at recommended doses of zaleplon (typically 5-20mg/before bed). Other sedatives/hypnotics have been associated with various signs and symptoms of a withdrawal syndrome, following abrupt discontinuation, ranging from mild dysphoria and insomnia to more serious cases that include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Following, abrupt cessation, the seizure threshold is further lowered, wherein coma and death are possible outcomes if untreated.
Zaleplon, like zolpidem, zopiclone or eszopiclone are all specific agonists at the benzodiazepine GABA-A α1 sub receptor site. It also modulates the GABA-A sub sites, α2 and α3, to a lesser degree. It has no statistical significance as an anticonvulsant. However, as a pyrazolopyrimidine, zaleplon has served as a novel chemical platform, from which new anxiolytics, will hopefully arise. Much like zolpidem, as an imidazopyridine and also a full agonist at the GABA-A α1 sub receptor site, has been reviewed considerably with some novel contributions. See: alpidem.
Zaleplon selectively binds with high efficacy to the benzodiazepine site (ω1) on the α1 containing GABA-A receptors which help produce the primary therapeutic hypnotic properties. The ultra-short half-life gives zaleplon a unique advantage over other hypnotics because of its lack of next day residual effects on driving and other performance related skills. Unlike non-selective benzodiazepine drugs and zopiclone which distort the sleep pattern, zaleplon appears to induce sleep without disrupting, the natural sleep architecture.
A meta-analysis of randomised controlled clinical trials which compared benzodiazepines against zaleplon or other "Z Drugs" such as zolpidem, zopiclone and eszopiclone has found that there are few clear and consistent differences between zaleplon and the benzodiazepines in terms of sleep onset latency, total sleep duration, number of awakenings, quality of sleep, adverse events, tolerance, rebound insomnia and daytime alertness.
Zaleplon has a pharmacological profile similar to benzodiazepines, that is characterized by an increase in slow wave deep sleep (SWDS) with rapid onset of hypnotic action. Zaleplon is a full agonist for the benzodiazepine α1 receptor located on the GABA-A receptor complex in the body, with lower affinity for the α2 and α3 sub sites. It selectively enhances the action of GABA similar to, but more selectively than benzodiazepines. Zaleplon, although not a benzodiazepine, maintains a very similar chemical structure nonetheless; known for inducing hypnotic effects via α1 sub receptor sites, anxiolytic and myorelaxant effects via α2 and α3 sub sites, with negligible anticonvulsant properties (via α5 sub site), as zaleplon action is modulated at benzodiazepine receptor sites. The elimination half-life of zaleplon is 1 hour. The absorption rate of zaleplon is rapid and the onset of therapeutic effects is typically breached within 5-15 minutes following ingestion.
Zaleplon should be understood as an ultra short acting sedative hypnotic drug for the treatment of insomnia. Zaleplon increases EEG power density in the delta frequency band and a decrease in the energy of the theta frequency band 
Pure zaleplon in its solid state is a white to off-white powder that has very low solubility in water as well as low solubility in alcohol and propylene glycol. It has a partition coefficient in octanol/water that is constant (log PC = 1.23) when the pH range is between 1 and 7.
Zaleplon is primarily metabolised by aldehyde oxidase, and its half-life can be affected by substances which inhibit or induce aldehyde oxidase. Taken orally, zaleplon reaches full concentration in approximately one hour. It is extensively metabolised, into 5-oxo-zaleplon and 5-oxo-desethylzaleplon (the latter via desethylzaleplon), with less than 1% of it excreted intact in urine.
Cimetidine (Tagamet in the US) alongside grapefruit, are known to increase blood plasma concentrations of benzodiazepines metabolized by the P450 CYP3A4 liver enzyme (e.g. alprazolam), as well as increasing the time by which the drug leaves the body, effectively extending the half life and enhancing effects, to potentially toxic levels. Thus, given the similarities between zaleplon and benzodiazepines, particularly in effect, and not just chemical structure, it is reasonable to take precautions (e.g. inquire at a pharmacy) before one consumes cimetidine (or grapefruit) while also taking zaleplon.
Smoking tobacco/ingesting nicotine as well as caffeine likely reduces blood plasma concentrations of zaleplon, as sedative-hypnotic efficacy is diminished. This impact is shared by all GABAergics, whether nonbenzodiazepines, benzodiazepines, barbiturates, carbamates, quinazolines or alcohol.
Recreational use 
Zaleplon (Sonata or Starnoc) has the potential to be a drug of abuse, but more probable is that individuals prescribed zaleplon may use it to better fit their needs/desires (e.g. patient is allowed to individually titrate their dose nightly to help reduce early morning awakenings). Sometimes, this use involves a different delivery method (insufflating) to induce effects faster.
Remaining cognizant of zaleplon's partial water solubility, the method of administration (RoA) that best delivers the entirety of any amount of zaleplon is via the mouth. Any other method, and zaleplon is simply being wasted, while likely damaging nasal passage-ways as well as the sinuses.
Though, one should remain mindful that a vast majority of benzodiazepine and non-benzodiazepine "Z drug" users do not abuse their medicine. Thus, while it is possible to 'abuse' zaleplon, it should not be presumed that the phenomenon is widespread or any notion that reformulation of the medicine, to prevent potential future abuse, is baseless.
More concerning than zaleplon, is combining alcohol with zaleplon. This combination, is synergistic and volatile once it has entered the bloodstream. Fatal respiratory depression and asphyxiation from vomiting when combined with alcohol, are the primary reasons why zaleplon is a substance of concern. Given alcohol's widespread popularity worldwide, it cannot be presumed that zaleplon is a dangerous substance, rather it is only dangerous in certain combinations or doses.
The mind and judgment altering effects of zaleplon are similar to those of many other benzodiazepines but the fast-acting nature and short half-life of the chemical mean that high dosages set on much more quickly and last for short periods of time (usually from 45 to 60 minutes). Insufflating the drug causes effects to happen even more quickly, and last for even shorter periods of time, with some loss of yield as zaleplon is not entirely water soluble. A common effect of zaleplon abuse is the occurrence of (typically short-lived ) hallucinations, commonly involving perceptions of nonexistent creatures. Though, compared to other non-benzodiazepines there are far less visual or audio hallucinations/disruptions, when compared with others in the class (e.g. zolpidem and the "Ambien Walrus"). Anterograde amnesia is a possibility, and can cause one to lose track of the amount of zaleplon already ingested, prompting one to ingest more than originally planned. However, continuous ingestion is extremely unlikely precisely because of zaleplon's quick onset of action.
See also 
- Z-drugs (excluding Zaleplon (Sonata))
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