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'{{short description|Medication}} {{More citations needed|date=June 2018}} {{Drugbox | Watchedfields = changed | verifiedrevid = 470635467 | IUPAC_name = ''N''-(3-(3-cyanopyrazolo[1,5-''a''] pyrimidin-7-yl)phenyl)-''N''-ethylacetamide | imageL = Zaleplon skeletal.svg | widthL = 110 | imageR = Zaleplon-from-xtal-Mercury-3D-bs.png | widthR = 180 <!--Clinical data--> | tradename = Sonata, Starnoc, Andante, others | Drugs.com = {{drugs.com|monograph|zaleplon}} | MedlinePlus = a601251 | pregnancy_US = N | legal_UK = Class C | legal_US = Schedule IV | routes_of_administration = Oral (medical), intranasal (recreational) <!--Pharmacokinetic data--> | bioavailability = 30% (oral) | metabolism = [[Hepatic]] | elimination_half-life = 1–1.5 h | excretion = [[Renal]] <!--Identifiers--> | IUPHAR_ligand = 4345 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 151319-34-5 | ATC_prefix = N05 | ATC_suffix = CF03 | PubChem = 5719 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00962 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 5517 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = S62U433RMH | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00530 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 10102 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1521 <!--Chemical data--> | C=17 | H=15 | N=5 | O=1 | smiles = O=C(C)N(CC)C1=CC=CC(C2=CC=NC3=C(C=NN23)C#N)=C1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C17H15N5O/c1-3-21(12(2)23)15-6-4-5-13(9-15)16-7-8-19-17-14(10-18)11-20-22(16)17/h4-9,11H,3H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = HUNXMJYCHXQEGX-UHFFFAOYSA-N }} '''Zaleplon''', sold under the brand names '''Sonata''' among others, is a [[sedative]]-[[hypnotic]], used to treat [[insomnia]]. It is a [[nonbenzodiazepine]] [[hypnotic]] from the [[pyrazolopyrimidine]] class.<ref>{{cite journal | vauthors = Elie R, Rüther E, Farr I, Emilien G, Salinas E | title = Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group | journal = The Journal of Clinical Psychiatry | volume = 60 | issue = 8 | pages = 536–44 | date = August 1999 | pmid = 10485636 | doi = 10.4088/JCP.v60n0806 }}</ref> It is manufactured by [[King Pharmaceuticals]] and [[Gedeon Richter Plc.]]. It has been discontinued in [[Canada]] but can be manufactured if a prescription is brought to a [[compounding pharmacy]].<ref>{{cite web|url=http://www.pacepharmacy.com/retailer/store_templates/ret_about_us.asp?storeID=1689ECD842A64B858C7535C97E925587|title=Pace Pharmacy – About Our Store|access-date=2015-06-18|archive-url=https://web.archive.org/web/20160304062437/http://www.pacepharmacy.com/retailer/store_templates/ret_about_us.asp?storeID=1689ECD842A64B858C7535C97E925587|archive-date=2016-03-04|url-status=dead}}</ref> It was prescribed rarely in the [[United Kingdom]], with [[zopiclone]] being the preferred [[Z-drug]] by the [[National Health Service]] (NHS)and is now unavailable. {{citation needed|date=December 2016}} == Medical uses == Zaleplon is slightly effective in insomnia,<ref name=TB2012>{{cite journal | vauthors = Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN | title = Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration | journal = BMJ | volume = 345 | pages = e8343 | date = December 2012 | pmid = 23248080 | pmc = 3544552 | doi = 10.1136/bmj.e8343 }}</ref> primarily characterized by difficulty falling asleep. Zaleplon significantly reduces the time required to fall asleep by improving sleep latency and may therefore facilitate sleep induction rather than sleep maintenance.<ref name="Bhandari 2020">{{Citation|last1=Bhandari|first1=Priyanka|title=Zaleplon|date=2020|url=http://www.ncbi.nlm.nih.gov/books/NBK551571/|work=StatPearls|place=Treasure Island (FL)|publisher=StatPearls Publishing|pmid=31855398|access-date=2020-07-08|last2=Sapra|first2=Amit}}</ref><ref>{{Cite journal|last1=Ebbens|first1=Marieke M|last2=Verster|first2=Joris C|date=2010-07-20|title=Clinical evaluation of zaleplon in the treatment of insomnia|journal=Nature and Science of Sleep|volume=2|pages=115–126|doi=10.2147/nss.s6853|issn=1179-1608|pmc=3630939|pmid=23616704}}</ref><ref name="Dooley 413–445">{{Cite journal|last1=Dooley|first1=M.|last2=Plosker|first2=G. L.|date=August 2000|title=Zaleplon: a review of its use in the treatment of insomnia|journal=Drugs|volume=60|issue=2|pages=413–445|doi=10.2165/00003495-200060020-00014|issn=0012-6667|pmid=10983740}}</ref> Due to its ultrashort elimination half-life, zaleplon may not be effective in reducing premature awakenings; however, it may be administered to alleviate middle-of-the-night awakenings.<ref name="Bhandari 2020"/> However, zaleplon has not been empirically shown to increase total sleep time.<ref name="Dooley 413–445"/><ref name="Bhandari 2020"/> 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.<ref>{{cite journal | vauthors = Verster JC, Veldhuijzen DS, Volkerts ER | title = Residual effects of sleep medication on driving ability | journal = Sleep Medicine Reviews | volume = 8 | issue = 4 | pages = 309–25 | date = August 2004 | pmid = 15233958 | doi = 10.1016/j.smrv.2004.02.001 | hdl = 1874/11902 | hdl-access = free }}</ref> It may have advantages over [[benzodiazepines]] with fewer adverse effects.<ref name=Bar2005>{{cite journal | vauthors = Barbera J, Shapiro C | title = Benefit-risk assessment of zaleplon in the treatment of insomnia | journal = Drug Safety | volume = 28 | issue = 4 | pages = 301–18 | year = 2005 | pmid = 15783240 | doi = 10.2165/00002018-200528040-00003 | s2cid = 24222535 }}</ref> Neither zaleplon, nor any nonbenzodiazepine hypnotic class medication should be combined with alcohol, as both [[Neuromodulation (biology)|modulate]] [[GABAA receptor|GABA_A]] receptor sites, and in a [[synergistic]] manner increase the chances of fatal [[respiratory depression]] and [[asphyxiation]] from vomiting.{{Citation needed|reason = |date=May 2014}} === Special populations === Zaleplon is not recommended for chronic use in the elderly.<ref>{{cite journal | title = American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults | journal = Journal of the American Geriatrics Society | volume = 60 | issue = 4 | pages = 616–31 | date = April 2012 | pmid = 22376048 | pmc = 3571677 | doi = 10.1111/j.1532-5415.2012.03923.x | author1 = American Geriatrics Society 2012 Beers Criteria Update Expert Panel }}</ref> 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.<ref>{{cite journal | vauthors = Antai-Otong D | title = The art of prescribing. Risks and benefits of non-benzodiazepine receptor agonists in the treatment of acute primary insomnia in older adults | journal = Perspectives in Psychiatric Care | volume = 42 | issue = 3 | pages = 196–200 | date = August 2006 | pmid = 16916422 | doi = 10.1111/j.1744-6163.2006.00070.x | url = http://www3.interscience.wiley.com/journal/118727940/abstract | archive-url = https://archive.today/20130106043709/http://www3.interscience.wiley.com/journal/118727940/abstract | url-status = dead | archive-date = 2013-01-06 }}</ref> When compared with [[benzodiazepines]], nonbenzodiazepines (including zaleplon) offer few significant advantages in efficacy and tolerability among elderly individuals. Long-term use of sedative/hypnotics for insomnia has traditionally been discouraged for reasons that include concerns about addiction and [[Rebound effect|rebound insomnia]], as well to the risk of side effects associated to GABA_A agonists, such as cognitive impairment, [[anterograde amnesia]], daytime sedation, musculoskeletal impairment, and subsequently an increased risk of harm to oneself (e.g. falling) and to others (e.g. [[Traffic collision|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 nothing concrete suggests long-term use poses any direct harm to a person.<ref name="Bain KT 2006 168–92">{{cite journal | vauthors = Bain KT | title = Management of chronic insomnia in elderly persons | journal = The American Journal of Geriatric Pharmacotherapy | volume = 4 | issue = 2 | pages = 168–92 | date = June 2006 | pmid = 16860264 | doi = 10.1016/j.amjopharm.2006.06.006 }}</ref> Still, as of today neither benzodiazepines nor nonbenzodiazepines are recommended for the long-term treatment of insomnia. == Adverse effects == The adverse effects of zaleplon are similar to the adverse effects of benzodiazepines, although with less next-day sedation,<ref name="Wagner J 1998 680–91">{{cite journal | vauthors = Wagner J, Wagner ML, Hening WA | title = Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia | journal = The Annals of Pharmacotherapy | volume = 32 | issue = 6 | pages = 680–91 | date = June 1998 | pmid = 9640488 | doi = 10.1345/aph.17111 | s2cid = 34250754 }}</ref> and in two studies zaleplon use was found not to cause an increase in traffic accidents, as compared to other [[hypnotics]] currently on the market.<ref>{{cite journal | vauthors = Menzin J, Lang KM, Levy P, Levy E | title = A general model of the effects of sleep medications on the risk and cost of motor vehicle accidents and its application to France | journal = PharmacoEconomics | volume = 19 | issue = 1 | pages = 69–78 | date = January 2001 | pmid = 11252547 | doi = 10.2165/00019053-200119010-00005 | s2cid = 45013069 }}</ref><ref>{{cite journal | vauthors = Vermeeren A, Riedel WJ, van Boxtel MP, Darwish M, Paty I, Patat A | title = Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol | journal = Sleep | volume = 25 | issue = 2 | pages = 224–31 | date = March 2002 | pmid = 11905433 }}</ref> Sleeping pills, including zaleplon, have been associated with an increased risk of death.<ref>{{cite journal |last1=Kripke |first1=DF |title=Mortality Risk of Hypnotics: Strengths and Limits of Evidence. |journal=Drug Safety |date=February 2016 |volume=39 |issue=2 |pages=93–107 |doi=10.1007/s40264-015-0362-0 |pmid=26563222|s2cid=7946506 |url=https://escholarship.org/content/qt08d9f3d5/qt08d9f3d5.pdf?t=nz1gjv }}</ref> Available data cannot provide a reliable estimate of the incidence of [[Substance dependence|dependence]] during treatment at recommended doses of zaleplon (typically 5–20&nbsp;mg before bed). Other sedative/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]], [[tremor]]s, and [[convulsions]]. Following abrupt cessation, the [[seizure threshold]] is further lowered, wherein [[coma]] and death are possible outcomes if untreated. Some evidence suggests zaleplon is not as chemically reinforcing and exhibits far fewer [[rebound effects]] when compared with other nonbenzodiazepines, or [[Z-drug]]s.<ref>{{cite journal | vauthors = Lader MH | title = Implications of hypnotic flexibility on patterns of clinical use | journal = International Journal of Clinical Practice. Supplement | issue = 116 | pages = 14–9 | date = January 2001 | pmid = 11219327 }}</ref> == Interactions == Cimetidine, [[rifampicin]], and [[thioridazine]] cause interactions with zaleplon.<ref>{{cite journal | vauthors = Wang JS, DeVane CL | title = Pharmacokinetics and drug interactions of the sedative hypnotics | journal = Psychopharmacology Bulletin | volume = 37 | issue = 1 | pages = 10–29 | year = 2003 | pmid = 14561946 | doi = 10.1007/BF01990373 | s2cid = 1543185 | url = http://www.medworksmedia.com/psychopharmbulletin/pdf/12/010-029_PB%20W03_Wang_final.pdf | access-date = 2008-12-28 | archive-url = https://web.archive.org/web/20070709230745/http://www.medworksmedia.com/psychopharmbulletin/pdf/12/010-029_PB%20W03_Wang_final.pdf | archive-date = 2007-07-09 | url-status = dead }}</ref> [[Cimetidine]] and [[Grapefruit drug interactions|grapefruit]] are known to increase [[blood plasma]] concentrations of benzodiazepines metabolized by the P450 [[CYP3A4]] [[liver enzyme]] (e.g. [[alprazolam]]) by extending 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. == Pharmacology == ===Mechanism of action=== GANDA MO! Zaleplon is a high-affinity ligand of positive modulator sites of GABA_A receptors, which enhances GABAergic inhibition of neurotransmission in the central nervous system. The ultrashort [[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.<ref>{{cite journal | vauthors = Patat A, Paty I, Hindmarch I | title = Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent | journal = Human Psychopharmacology | volume = 16 | issue = 5 | pages = 369–392 | date = July 2001 | pmid = 12404558 | doi = 10.1002/hup.310 | s2cid = 21096374 }}</ref><ref>{{cite journal | vauthors = Rowlett JK, Spealman RD, Lelas S, Cook JM, Yin W | title = Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors | journal = Psychopharmacology | volume = 165 | issue = 3 | pages = 209–15 | date = January 2003 | pmid = 12420154 | doi = 10.1007/s00213-002-1275-z | s2cid = 37632215 }}</ref> Unlike nonselective benzodiazepine drugs and zopiclone, which distort the [[sleep pattern]], zaleplon appears to induce sleep without disrupting the natural [[sleep architecture]].<ref>{{cite journal | vauthors = Noguchi H, Kitazumi K, Mori M, Shiba T | title = Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic | journal = European Journal of Pharmacology | volume = 434 | issue = 1–2 | pages = 21–8 | date = January 2002 | pmid = 11755161 | doi = 10.1016/S0014-2999(01)01502-3 }}</ref> A [[meta-analysis]] of randomized, controlled [[clinical trials]] which compared benzodiazepines against zaleplon or other Z-drugs such as zolpidem, zopiclone, and eszopiclone has found 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, [[Drug tolerance|tolerance]], [[rebound insomnia]], and daytime [[alertness]].<ref>{{cite journal | vauthors = Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T | title = Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis | journal = Human Psychopharmacology | volume = 19 | issue = 5 | pages = 305–22 | date = July 2004 | pmid = 15252823 | doi = 10.1002/hup.594 | s2cid = 10888200 }}</ref> Zaleplon has a pharmacological profile similar to benzodiazepines, 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 subsites. It selectively enhances the action of [[gamma-Aminobutyric acid|GABA]] similar to, but more selectively than benzodiazepines. Zaleplon, although not a benzodiazepine, maintains a very similar pharmacological profile nonetheless, known for inducing hypnotic effects by α₁ subreceptor sites, anxiolytic and [[muscle relaxant]] effects via α₂ and α₃ subsites, with negligible [[anticonvulsant]] properties (via α₅ subsite), as zaleplon action is [[modulated]] at benzodiazepine receptor sites. The [[elimination half-life]] of zaleplon is about 1–1.5 hours. 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 ultrashort-acting sedative-hypnotic drug for the treatment of insomnia. Zaleplon increases [[EEG]] power density in the δ-frequency band and a decrease in the energy of the θ-frequency band<ref>{{cite journal | vauthors = Noguchi H, Kitazumi K, Mori M, Shiba T | title = Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats | journal = Journal of Pharmacological Sciences | volume = 94 | issue = 3 | pages = 246–51 | date = March 2004 | pmid = 15037809 | doi = 10.1254/jphs.94.246 | url = http://www.jstage.jst.go.jp/article/jphs/94/3/246/_pdf | format = pdf | doi-access = free }}</ref><ref>{{cite journal | vauthors = Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, Foster AC | title = Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 317 | issue = 1 | pages = 369–77 | date = April 2006 | pmid = 16399882 | doi = 10.1124/jpet.105.096701 | s2cid = 46510829 }}</ref> === Pharmacokinetics === 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 about one hour. It is extensively metabolised into 5-oxozaleplon and 5-oxodesethylzaleplon (the latter via desethylzaleplon), with less than 1% of it excreted intact in urine. == Chemistry == Pure zaleplon in its solid state is a white to off-white powder with very low [[solubility]] in water, as well as low solubility in [[ethanol]] and [[propylene glycol]]. It has a constant [[octanol-water partition coefficient]] of log P = 1.23 in the [[pH]] range between 1 and 7. It is classified as a [[pyrazolopyrimidine]].<ref name="PubChemZaleplon">{{cite web |title=Zaleplon |url=https://pubchem.ncbi.nlm.nih.gov/compound/zaleplon |website=pubchem.ncbi.nlm.nih.gov |publisher=U.S. National Library of Medicine |access-date=10 June 2018 |language=en}}</ref> === Synthesis === [[File:Zaleplon synthesis.svg|thumb|center|900px|Zaleplon synthesis<ref>J. P. Dusza et al., {{US patent|4626538}} (1986 to Am. Cyanamid).</ref><ref>http://en.cnki.com.cn/Article_en/CJFDTotal-ZYSG200205002.htm 《China Pharmacist》 2002-05 Synthesis of Zaleplon.</ref>]] The synthesis starts with the condensation of [[3-acetylacetanilide]]<ref>{{cite journal | vauthors = Banasik M, Komura H, Shimoyama M, Ueda K | title = Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase | journal = The Journal of Biological Chemistry | volume = 267 | issue = 3 | pages = 1569–75 | date = January 1992 | pmid = 1530940 }}</ref><ref>{{cite journal | vauthors = Dehmel F, Weinbrenner S, Julius H, Ciossek T, Maier T, Stengel T, Fettis K, Burkhardt C, Wieland H, Beckers T | title = Trithiocarbonates as a novel class of HDAC inhibitors: SAR studies, isoenzyme selectivity, and pharmacological profiles | journal = Journal of Medicinal Chemistry | volume = 51 | issue = 13 | pages = 3985–4001 | date = July 2008 | pmid = 18558669 | doi = 10.1021/jm800093c }}</ref> ('''1''') with ''N'',''N''-dimethylformamide dimethyl acetal ([[DMFDMA]])<ref>{{Cite journal |doi=10.1021/jo00193a045|title = Convenient preparation of N,N-dimethylacetamide dimethyl acetal|journal = The Journal of Organic Chemistry|volume = 49|issue = 19|pages = 3659|year = 1984|last1 = Salomon|first1 = Robert G.|last2 = Raychaudhuri|first2 = Swadesh R.}}</ref> to give the eneamide ('''2'''). The anilide nitrogen is then alkylated by means of [[sodium hydride]] and [[ethyl iodide]] to give '''3'''. The first step in the condensation with 3-amino-4-cyanopyrazole can be visualized as involving an [[addition-elimination reaction]] sequence on the eneamide function to give a transient intermediate such as '''5'''. Cyclization then leads to formation of the fused [[pyrimidine]] ring to afford zaleplon ('''6'''). ==Society and culture== === Recreational use === Zaleplon has the potential to be a drug of recreational use, and has been found to have an addictive potential similar to benzodiazepine and benzodiazepine-like hypnotics.<ref>{{cite web|url=http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=6299|title=Sonata®(zaleplon)Capsules}}</ref> The mind- and judgment-altering effects of zaleplon are similar to those of many benzodiazepines, but the fast-acting nature and short half-life of the chemical mean high doses set on much more quickly and last for short periods of time (usually from 45 to 60 minutes). Some individuals use a different delivery method than prescribed, such as [[Insufflation (medicine)|insufflation]], to induce effects faster.<ref>{{cite journal | vauthors = Paparrigopoulos T, Tzavellas E, Karaiskos D, Liappas I | title = Intranasal zaleplon abuse | journal = The American Journal of Psychiatry | volume = 165 | issue = 11 | pages = 1489–90 | date = November 2008 | pmid = 18981079 | doi = 10.1176/appi.ajp.2008.08030452 | url = http://ajp.psychiatryonline.org/cgi/content/full/165/11/1489-a }}</ref> [[File:Sonata10mg.JPG|thumb|right|180px| Sonata 10-mg capsules]] A common effect of recreational zaleplon use is the occurrence of (typically short-lived) [[hallucinations]]. Fewer visual and auditory hallucinations/disruptions occur with the use of zaleplon than with other [[Z-drug]]s, like [[zolpidem]]. {{Citation needed|date=February 2013}} [[Anterograde amnesia]] can occur and can cause one to lose track of the amount of zaleplon already ingested, prompting the ingesting of more than originally planned.<ref>{{cite journal | vauthors = Rush CR, Frey JM, Griffiths RR | title = Zaleplon and triazolam in humans: acute behavioral effects and abuse potential | journal = Psychopharmacology | volume = 145 | issue = 1 | pages = 39–51 | date = July 1999 | pmid = 10445371 | doi = 10.1007/s002130051030 | s2cid = 12061258 }}</ref><ref>{{cite journal | vauthors = Ator NA | title = Zaleplon and triazolam: drug discrimination, plasma levels, and self-administration in baboons | journal = Drug and Alcohol Dependence | volume = 61 | issue = 1 | pages = 55–68 | date = December 2000 | pmid = 11064184 | doi = 10.1016/S0376-8716(00)00123-X }}</ref> However, continuous ingestion is extremely unlikely precisely because of zaleplon's quick onset of action. The combination of alcohol and zaleplon can result in fatal [[respiratory depression]] and [[asphyxiation]] from vomiting.{{Citation needed|reason = |date = August 2013}} === Aviation use === The [[Federal Aviation Administration]] allows zaleplon with a 12-hour wait period and no more than twice a week, which makes it the sleep medication with the shortest allowed waiting period after use.<ref name=aviationMedicine>{{cite web|url=https://www.aviationmedicine.com/medication-database|title=Medication Database – AMAS}}</ref> The substances with the 2nd shortest period, which is of 24 hours, are zolpidem and [[ramelteon]].<ref name=aviationMedicine /> === Military use === The [[United States Air Force]] uses zaleplon as one of the hypnotics approved as a "[[no-go pill]]" to help aviators and special-duty personnel sleep in support of mission readiness (with a four-hour restriction on subsequent flight operation). "Ground tests" are required prior to authorization being issued to use the medication in an operational situation.<ref name=Caldwell>{{cite journal | vauthors = Caldwell JA, Caldwell JL | title = Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures | journal = Aviation, Space, and Environmental Medicine | volume = 76 | issue = 7 Suppl | pages = C39-51 | date = July 2005 | pmid = 16018329 | url = http://docserver.ingentaconnect.com/deliver/connect/asma/00956562/v76n7x1/s10.pdf?expires=1335744234&id=68546495&titleid=8218&accname=Guest+User&checksum=D97BA65A8E7071CC3766CF365ED85FA3 | format = pdf }}</ref> The other hypnotics used as "no-go pills" are [[temazepam]] and [[zolpidem]], which both have longer mandatory recovery periods.<ref name=Caldwell /> == See also == {{div col|colwidth=22em}} * [[Cyclopyrrolones]] * [[Eszopiclone]] * [[Imidazopyridines]] * [[Indiplon]] * [[Necopidem]] * [[Ocinaplon]] * [[Pagoclone]] * [[Pyrazolopyrimidines]] {{div col end}} == References == {{Reflist|2}} {{Hypnotics and sedatives}} {{Insomnia pharmacotherapies}} {{GABAAR PAMs}} [[Category:Acetanilides]] [[Category:GABAA receptor positive allosteric modulators]] [[Category:Nitriles]] [[Category:Pfizer brands]] [[Category:Nonbenzodiazepines]] [[Category:Pyrazolopyrimidines]]'