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'{{Drugbox| |IUPAC_name = ''N''-(3-(3-cyanopyrazolo[1,5-''a''] pyrimidin-7-yl)phenyl)-''N''- ethylacetamide | image = Zaleplon skeletal.svg | width=140 | CAS_number= 151319-34-5 | ATC_prefix=N05 | ATC_suffix=CF03 | ATC_supplemental= | PubChem=5719 | DrugBank=APRD00411 | C=17 | H=15 | N=5 | O=1 | molecular_weight = 305.34 | bioavailability= 30% (oral) | metabolism = [[Hepatic]] | elimination_half-life= 1 hour | excretion = [[Renal]] | pregnancy_US = C | legal_US = Schedule IV | routes_of_administration= Oral }} '''Zaleplon''' (marketed under the brand names '''Sonata''' and '''Starnoc''') is a [[sedative]]/[[hypnotic]], mainly used for [[insomnia]]. It is a [[nonbenzodiazepine]] [[hypnotic]] from the [[pyrazolopyrimidine]] class.<ref>{{cite journal | journal=J Clin Psychiatry | year=1999 |month=Aug | pages=536–44 | title=Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group | author=Elie R | coauthors=Rüther E, Farr I, Emilien G, Salinas E | pmid=10485636 }}</ref> Zaleplon is one of few sleep medications which have been found to not cause an increase in road traffic accidents, thus demonstrating a much higher safety profile than many other [[hypnotics]] currently on the market.<ref>{{cite journal |author=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 |year=2001 |month=January |pmid=11252547 |doi= 10.2165/00019053-200119010-00005|url=}}</ref><ref>{{cite journal |author=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 |year=2002 |month=March |pmid=11905433 |doi= |url=}}</ref> Sonata (US) is manufactured by King Pharm. of Bristol, TN; Starnoc has been discontinued in Canada. ==Chemistry== 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. ==Clinical uses== Zaleplon is efficacious in the treatment of insomnia where difficulty in falling asleep is the primary complaint. Zaleplon, unlike many other hypnotic drugs, does not interfere with sleep architecture and can be administered for up to 5 weeks without the risk of dependence or rebound insomnia upon discontinuation.<ref>{{cite journal | journal =Sleep Med | year =2000 |month=February | pages =41–49 | title =A five week, polysomnographic assessment of zaleplon 10 mg for the treatment of primary insomnia | author =Walsh JK | coauthors =Vogel GW, Scharf M, Erman M, William Erwin C , Schweitzer PK, Mangano RM, Roth T | pmid =10733619 | doi =10.1016/S1389-9457(99)00006-4 | volume =1 }}</ref> Zaleplon is also efficacious in the treatment of [[middle of the night insomnia]] without causing residual hangover effects.<ref>{{cite journal | journal =Clin Neuropharmacol | year=2000 |month=Jan-Feb | pages =17–21 | title =Lack of residual sedation following middle-of-the-night zaleplon administration in sleep maintenance insomnia | author =Walsh JK | coauthors =Pollak CP, Scharf MB, Schweitzer PK, Vogel GW | pmid =10682226 | doi =10.1097/00002826-200001000-00004 | volume =23 }}</ref><ref>{{cite journal |author=Verster JC, Veldhuijzen DS, Volkerts ER |title=Residual effects of sleep medication on driving ability |journal=Sleep Med Rev |volume=8 |issue=4 |pages=309–25 |year=2004 |month=August |pmid=15233958 |doi=10.1016/j.smrv.2004.02.001 |url=http://linkinghub.elsevier.com/retrieve/pii/S1087079204000073}}</ref> Zaleplon has advantages over [[benzodiazepines]] in that it does not disrupt [[sleep architecture]] unlike benzodiazepines which whilst inducing sleep actually worsen the quality of it.<ref>{{cite journal |author=Barbera J, Shapiro C |title=Benefit-risk assessment of zaleplon in the treatment of insomnia |journal=Drug Saf |volume=28 |issue=4 |pages=301–18 |year=2005 |pmid=15783240 |doi= 10.2165/00002018-200528040-00003|url=}}</ref> ==Pharmacology== Zaleplon selectively binds with high efficacy to the benzodiazepine site (ω₁) on the α₁ containing [[GABA receptors|GABA_A receptors]] which produces its 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.<ref>{{cite journal |author=Patat A, Paty I, Hindmarch I |title=Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent |journal=Hum Psychopharmacol |volume=16 |issue=5 |pages=369–392 |year=2001 |month=July |pmid=12404558 |doi=10.1002/hup.310}}</ref><ref>{{cite journal |author=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 (Berl.) |volume=165 |issue=3 |pages=209–15 |year=2003 |month=January |pmid=12420154 |doi=10.1007/s00213-002-1275-z |url=http://www.springerlink.com/content/392vkmeej4at9yuy/fulltext.pdf |format=PDF}}</ref> Unlike non-selective [[benzodiazepine]] drugs and zopiclone which distort the sleep pattern zaleplon appears to induce sleep without disrupting the natural sleep architecture.<ref>{{cite journal |author=Noguchi H, Kitazumi K, Mori M, Shiba T |title=Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic |journal=Eur. J. Pharmacol. |volume=434 |issue=1-2 |pages=21–8 |year=2002 |month=January |pmid=11755161 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0014299901015023}}</ref> A [[meta-analysis]] of randomised controlled [[clinical trials]] which compared benzodiazepines against Zaleplon or other Z Drugs such as [[zolpidem]] and [[zopiclone]], 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.<ref>{{cite journal | last = Dündar | first = Y | coauthors = Dodd S, Strobl J, Boland A, Dickson R, Walley T. | year = 2004 | month = July | title = Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis | journal = Hum Psychopharmacol. | volume = 19 | issue = 5 | pages = 305–22 | pmid = 15252823 | doi = 10.1002/hup.594 }}</ref> Zaleplon has a pharmacological profile similar to benzodiazepines, that is characterized by an increase in SWDS with rapid onset of hypnotic action. Zaleplon is a full agonist for the [[benzodiazepine]] α1 receptor located on the GABA_A receptor ionophore complex in the brain, with lower affinity for the α2 and α3 subtypes. It selectively enhances the action of GABA similar to but more selectively than [[benzodiazepines]]. Zaleplon, although not benzodiazepine-like in chemical structure induces sedative-hypnotic, anticonvulsant and anticonflict effects via its binding to the central nervous system (CNS) type benzodiazepine receptors. The [[elimination half life]] of zaleplon is 1 hour irrespective of dose. Absorption is rapid. Zaleplon can be classed as an ultra short acting sedative hypnotic drug for the treatment of insomnia characterised by difficulty in falling asleep. Zaleplon increases [[EEG]] power density in the delta frequency band and a decrease in the energy of the theta frequency band. In tests on rabbits zaleplon shows drowsy pattern of spontaneous EEG characterized by high-voltage slow waves and desynchronization of hippocampal theta waves and an increase in the energy of the delta frequency band on the spectral analysis of the electroencephalogram.<ref>{{cite journal | author = Noguchi H | coauthors = Kitazumi K, Mori M, Shiba T. | year = 2004 | month = March | title = Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats | journal = J Pharmacol Sci. | volume = 94 | issue = 3 | pages = 246–51 | pmid = 15037809 | url = http://www.jstage.jst.go.jp/article/jphs/94/3/246/_pdf | format = pdf | doi = 10.1254/jphs.94.246 }}</ref><ref>{{cite journal |author=Petroski RE, Pomeroy JE, Das R, ''et al'' |title=Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors |journal=J. Pharmacol. Exp. Ther. |volume=317 |issue=1 |pages=369–77 |year=2006 |month=April |pmid=16399882 |doi=10.1124/jpet.105.096701 |url=http://jpet.aspetjournals.org/cgi/content/full/317/1/369 |format=PDF}}</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 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. ==Elderly== An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, the [[nonbenzodiazepine]] (including zaleplon) sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment ([[anterograde amnesia]]), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia.<ref>{{cite journal | journal = Am J Geriatr Pharmacother | year = 2006 | month = June | volume = 4 | issue = 2 | pages = 168–92 | title = Management of chronic insomnia in elderly persons | author = Bain KT | pmid = 16860264 | doi = 10.1016/j.amjopharm.2006.06.006}}</ref> ==Side-effects== The side effects of zaleplon are similar to the side effects of benzodiazepines.<ref>{{cite journal | journal =Ann Pharmacother | year =1998 | pages =680–91 | month =June | title =Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia | author =Wagner J | coauthors =Wagner ML, Hening WA | pmid =9640488 }}</ref> Zaleplon may cause [[hallucinations]], abnormal behavior, severe [[mental confusion|confusion]], day-time drowsiness, [[dizziness]] or lightheadedness, unsteadiness and/or falls, [[double vision]] or other vision problems, agitation, [[headache]], [[nausea]], [[vomiting]], [[diarrhea]] or [[abdominal pain]], [[depression (mood)|depression]], [[muscle weakness]], [[tremor]], vivid or abnormal [[dream]]s and memory difficulties or [[amnesia]]. Zaleplon is habit-forming, meaning [[addiction]] or [[drug dependence]] may occur. Stopping this medication suddenly after prolonged or frequent use may cause withdrawal effects such as mood changes, anxiety, restlessness or [[rebound insomnia]].<ref>{{cite journal | journal=J Am Pharm Assoc (Wash) | year=1999 |month=Sep-Oct | pages=688–96 | title=Management of insomnia | author=Kirkwood CK | pmid=10533351 }}</ref> ==Special precautions== The elderly are more sensitive to the adverse effects of zaleplon such as cognitive side effects. Zaleplon may increase the risk of falls in the elderly.<ref>{{cite journal |author=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=Perspect Psychiatr Care |volume=42 |issue=3 |pages=196–200 |year=2006 |month=August |pmid=16916422 |doi=10.1111/j.1744-6163.2006.00070.x |url=http://www3.interscience.wiley.com/journal/118727940/abstract}}</ref> ==Interactions== [[Cimetidine]], [[rifampicin]] and [[thioridazine]] cause interactions with zaleplon.<ref>{{cite journal |author=Wang JS, DeVane CL |title=Pharmacokinetics and drug interactions of the sedative hypnotics |journal=Psychopharmacol Bull |volume=37 |issue=1 |pages=10–29 |year=2003 |pmid=14561946 |doi= |url=http://www.medworksmedia.com/psychopharmbulletin/pdf/12/010-029_PB%20W03_Wang_final.pdf |format=PDF}}</ref> ==Recreational use== Zaleplon (Sonata) has a relatively high potential to be abused. Often this use involves a different delivery method (insufflation) to induce effects faster. [[Image:Sonata10mg.JPG|thumb|right|180px|A one month's supply of Sonata 10mg capsules.]] Zaleplon misuse has similar drug liking properties, adverse effects and monetary street value as benzodiazepines.<ref>{{cite journal | journal=Psychopharmacology (Berl) | year=1999 |month=Jul | pages=39–51 | title=Zaleplon and triazolam in humans: acute behavioral effects and abuse potential | author=Rush CR | coauthors=Frey JM, Griffiths RR | pmid=10445371 | doi=10.1007/s002130051030 | volume=145 }}</ref><ref>{{cite journal | journal=Drug Alcohol Depend | year=2000 | pages=55–68 | title=Zaleplon and triazolam: drug discrimination, plasma levels, and self-administration in baboons | author=Ator NA | pmid=11064184 | doi=10.1016/S0376-8716(00)00123-X | volume=61 }}</ref> ==See also== *[[Nonbenzodiazepine]] *[[Zolpidem]] *[[Zopiclone]] ==References== {{Reflist}} {{-}} {{Hypnotics and sedatives}} [[Category:Hypnotics]] [[Category:Pyrazolopyrimidines]] [[Category:Sedatives]] [[de:Zaleplon]] [[es:Zaleplon]] [[pl:Zaleplon]] [[sv:Zaleplon]]'