Zaleplon

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Zaleplon
Zaleplon skeletal.svg Zaleplon-from-xtal-Mercury-3D-bs.png
Clinical data
Trade names Sonata, others
AHFS/Drugs.com Monograph
MedlinePlus a601251
License data
Addiction
liability 		Moderate
Routes of
administration 		By mouth
Drug class nonbenzodiazepine
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 30% (oral) [4]
Metabolism Liver aldehyde oxidase (91%), CYP3A4 (9%) [5]
Metabolites No active metabolites [6]
Onset of action 10 to 30 minutes [7]
Elimination half-life 1 hr [4]
Duration of action Approximately 4 to 6 hours [7] [8] [9]
Excretion Kidney
Identifiers
  • N-(3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.126.674 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H15N5O
Molar mass 305.341 g·mol−1
3D model (JSmol)
  • CCN(C(C)=O)c1cccc(-c2ccnc3c(C#N)cnn23)c1
  • InChI=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 Yes check.svgY
  • Key:HUNXMJYCHXQEGX-UHFFFAOYSA-N Yes check.svgY
   (verify)

Zaleplon, sold under the brand name Sonata among others, is a sedative and hypnotic which is used to treat insomnia. It is a nonbenzodiazepine or Z-drug of the pyrazolopyrimidine class. [10] It was developed by King Pharmaceuticals and approved for medical use in the United States in 1999. [3]

Contents

Medical uses

Zaleplon is slightly effective in treating insomnia, [11] 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. [12] [13] [14] 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. [12] However, zaleplon has not been empirically shown to increase total sleep time. [14] [12]

Zaleplon does not significantly affect driving performance the morning following bedtime administration or 4 hours after middle-of-the-night administration. [15] It may have advantages over benzodiazepines with fewer adverse effects. [16]

Special populations

Zaleplon is not recommended for chronic use in the elderly. [17] 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 during pregnancy or lactation. Clinicians should devote more attention when prescribing for patients with a history of alcohol or drug abuse, psychotic illness, or depression. [18]

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. [19]

Adverse effects

The adverse effects of zaleplon are similar to the adverse effects of benzodiazepines, although with less next-day sedation, [20] 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. [21] [22]

Sleeping pills, including zaleplon, have been associated with an increased risk of death. [23]

Some evidence suggests zaleplon is not as chemically reinforcing and exhibits far fewer rebound effects when compared with other nonbenzodiazepines, or Z-drugs. [24]

Interactions

The CYP3A4 liver enzyme is a minor metabolic pathway for zaleplon, normally metabolizing about 9% of the drug. [5] CYP3A4 inducers such as rifampicin, phenytoin, carbamazepine, and phenobarbital can reduce the effectiveness of zaleplon, and therefore the FDA suggests that other hypnotic drugs be considered in patients taking a CYP3A4 inducer. [5]

Additional sedation has been observed when zaleplon is combined with thioridazine, but it is not clear whether this was due to merely an additive effect of taking two sedative drugs at once or a true drug-drug interaction. [25] Diphenhydramine, a weak inhibitor of aldehyde oxidase, has not been found to affect the pharmacokinetics of zaleplon. [25]

Pharmacology

Mechanism of action

Zaleplon is a high-selectivity, [26] high-affinity ligand of positive modulatory benzodiazepine sites on GABAA receptors. Zaleplon binds preferentially at benzodiazepine sites on α1-containing GABAA receptors (previously known as BZ1/Ω1 receptors), which largely mediate the sedative effects of benzodiazepines. [27] However, unlike zolpidem, zaleplon binds with appreciable affinity to benzodiazepine sites on some α2 and α3-containing GABAA receptors, which are implicated in the anxiolytic and muscle relaxant effects of benzodiazepines. Zaleplon demonstrates greater selectivity at these sites than lorazepam or zopiclone. [28] [29]

Unlike nonselective benzodiazepine drugs and zopiclone, which distort the sleep pattern, zaleplon appears to induce sleep without disrupting the normal sleep architecture. [30]

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, tolerance, rebound insomnia, and daytime alertness. [31]

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. [32] [33] In contrast to non-selective benzodiazepine drugs and zopiclone, zaleplon does not increase power in the β-frequency band. [34]

Pharmacokinetics

The ultrashort 1hr 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. [35] [36]

Zaleplon is primarily metabolised by aldehyde oxidase into 5-oxozaleplon, and its half-life may be affected by substances which inhibit or induce aldehyde oxidase. According to urine analysis, about 9% of zaleplon is metabolized by CYP3A4 to form desethylzaleplon, which is quickly metabolized by aldehyde oxidase to 5-oxodesethylzaleplon. [5] [4] All of these metabolites are inactive. [4] When taken orally, zaleplon reaches maximum concentration in about 45 minutes. [4]

Chemistry

Zaleplon is classified as a pyrazolopyrimidine. [37] 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. [5] It has a constant octanol-water partition coefficient of log P = 1.23 in the pH range between 1 and 7. [5]

Synthesis

Zaleplon synthesis Zaleplon synthesis.svg
Zaleplon synthesis

The synthesis starts with the condensation of 3-acetylacetanilide [40] [41] (1) with N,N-dimethylformamide dimethyl acetal (DMFDMA) [42] 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 the 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. [43]

Some individuals use a different delivery method than prescribed, such as insufflation, to induce effects faster. [44]

Sonata 10-mg capsules Sonata10mg.JPG
Sonata 10-mg capsules

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. [45] [46]

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. [47] The substances with the 2nd shortest period, which is of 24 hours, are zolpidem and ramelteon. [47]

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. [48] The other hypnotics used as "no-go pills" are temazepam and zolpidem, which both have longer mandatory recovery periods. [48]

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially known as "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche, which followed with the development of diazepam (Valium) three years later, in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Hypnotic</span> Drug whose use induces sleep

Hypnotic, or soporific drugs, commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to induce sleep and to treat insomnia (sleeplessness).

<span class="mw-page-title-main">Zolpidem</span> Hypnotic medication

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Flumazenil</span> GABA receptor antagonist drug and benzodiazepine antidote

Flumazenil is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines, through competitive inhibition.

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine, specifically a cyclopyrrolone, used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do inducing sedation but not with the anti-anxiety properties of the benzodiazepines.

<span class="mw-page-title-main">Flurazepam</span> Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals, was one of the first benzodiazepine hypnotic medications to be marketed.

<span class="mw-page-title-main">Eszopiclone</span> Hypnotic medication

Eszopiclone, sold under the brand name Lunesta among others, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken by mouth.

<span class="mw-page-title-main">Nonbenzodiazepine</span> Class of psychoactive drugs

Nonbenzodiazepines, sometimes referred to colloquially as Z-drugs, are a class of psychoactive, depressant, sedative, hypnotic, anxiolytic drugs that are benzodiazepine-like in uses, such as for treating insomnia and anxiety.

<span class="mw-page-title-main">Quazepam</span> Benzodiazipine

Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

<span class="mw-page-title-main">Estazolam</span> Triazolobenzodiazepine tranquilizer drug

Estazolam, sold under the brand name Prosom among others, is a tranquilizer medication of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Estazolam is an intermediate-acting oral benzodiazepine. It is used for short-term treatment of insomnia.

<span class="mw-page-title-main">Alpidem</span> Anxiolytic medication

Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.

<span class="mw-page-title-main">Lormetazepam</span> Benzodiazepine medication

Lormetazepam, sold under the brand name Noctamid among others, is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative and temazepam analogue. It possesses hypnotic, anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties.

<span class="mw-page-title-main">Bretazenil</span> Chemical compound

Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.

<span class="mw-page-title-main">Ocinaplon</span> Chemical compound

Ocinaplon is an anxiolytic drug in the pyrazolopyrimidine family of drugs. Other pyrazolopyrimidine drugs include zaleplon and indiplon.

<span class="mw-page-title-main">L-838,417</span> Chemical compound

L-838,417 is an anxiolytic drug used in scientific research. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. The compound was developed by Merck, Sharp and Dohme.

<span class="mw-page-title-main">CL-218,872</span> Chemical compound

CL-218,872 is a sedative and hypnotic drug used in scientific research. It has similar effects to sedative-hypnotic benzodiazepine drugs such as triazolam, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic.

<span class="mw-page-title-main">SX-3228</span> Chemical compound

SX-3228 is a sedative and hypnotic drug used in scientific research. It has similar effects to sedative-hypnotic benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

<span class="mw-page-title-main">Somnifacient</span> Class of medications that induce sleep

Somnifacient, also known as sedatives or sleeping pills, is a class of medications that induces sleep. It is mainly used for treatment of insomnia. Examples of somnifacients include benzodiazepines, barbiturates and antihistamines.

References

  1. ↑ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. 1 2 "Sonata (zaleplon) Capsules CIV". DailyMed. U.S. National Library of Medicine. Retrieved 21 March 2023.
  4. 1 2 3 4 5 Rosen AS, Fournié P, Darwish M, Danjou P, Troy SM (April 1999). "Zaleplon pharmacokinetics and absolute bioavailability". Biopharmaceutics & Drug Disposition. 20 (3): 171–175. doi:10.1002/(sici)1099-081x(199904)20:3<171::aid-bdd169>3.0.co;2-k. PMID   10211871.
  5. 1 2 3 4 5 6 "20859 S009, 011 FDA Approved Labeling Text 12.10.07" (PDF). FDA . Retrieved 21 March 2023.
  6. ↑ Coke JM, Edwards MD (April 2009). "Minimal and moderate oral sedation in the adult special needs patient". Dental Clinics of North America. 53 (2): 221–30, viii. doi:10.1016/j.cden.2008.12.005. PMID   19269393. Zaleplon (Sonata) has the shortest half-life of the Z-drugs of 1 hour and reaches peak plasma level in 1 hour. It is rapidly absorbed in under1 hour and has no active metabolites. The recommended adult dose is 5–20 mg.
  7. 1 2 Bechtel LK, Holstege CP (May 2007). "Criminal poisoning: drug-facilitated sexual assault". Emergency Medicine Clinics of North America. 25 (2): 499–525, abstract x. doi:10.1016/j.emc.2007.02.008. PMID   17482030. Zaleplon is available as an immediate-release tablet or capsule. An average oral dose of 10 to 15 mg has a rapid onset of clinical symptoms of approximately 10 to 30 minutes. Although the t1/2 for zaleplon is about 1 hour, the duration of clinical effects may persist for greater than 6 hours. This persistence may be because of the higher affinity of zaleplon for specific α2 and α3 subunits of the GABA receptor, unlike zolpidem or zopiclone [74].
  8. ↑ "SONATA - zaleplon capsule". DailyMed. U.S. National Library of Medicine. Retrieved 31 August 2024. Do not take Sonata unless you are able to get 4 or more hours of sleep before you must be active again. DO NOT use alcohol while taking Sonata or any other sleep medicine. Be sure to tell your physician if you suffer from depression. Sonata works very quickly. You should only take Sonata immediately before going to bed or after you have gone to bed and are having difficulty falling asleep. For Sonata to work best, you should not take Sonata with or immediately after a high-fat/heavy meal. Some people should start with the lowest dose (5 mg) of Sonata; these include the elderly (ie, ages 65 and over) and people with liver disease.
  9. ↑ Khouzam HR, Gill TS, Tan DT (2007). "The Patient with Posttraumatic Stress Disorder". Handbook of Emergency Psychiatry. Elsevier. pp. 453–473. doi:10.1016/b978-0-323-04088-4.50026-x. ISBN   978-0-323-04088-4. The adult dose is 10 mg, and 5 mg for geriatric patients.
  10. ↑ Elie R, Rüther E, Farr I, Emilien G, Salinas E (August 1999). "Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group". The Journal of Clinical Psychiatry. 60 (8): 536–44. doi:10.4088/JCP.v60n0806. PMID   10485636.
  11. ↑ Huedo-Medina TB, Kirsch I, Middlemass J, Klonizakis M, Siriwardena AN (December 2012). "Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: meta-analysis of data submitted to the Food and Drug Administration". BMJ. 345: e8343. doi:10.1136/bmj.e8343. PMC   3544552 . PMID   23248080.
  12. 1 2 3 Bhandari P, Sapra A (2020). "Zaleplon". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   31855398 . Retrieved 8 July 2020.
  13. ↑ Ebbens MM, Verster JC (20 July 2010). "Clinical evaluation of zaleplon in the treatment of insomnia". Nature and Science of Sleep. 2: 115–126. doi: 10.2147/nss.s6853 . PMC   3630939 . PMID   23616704.
  14. 1 2 Dooley M, Plosker GL (August 2000). "Zaleplon: a review of its use in the treatment of insomnia". Drugs. 60 (2): 413–445. doi:10.2165/00003495-200060020-00014. PMID   10983740. S2CID   195691571.
  15. ↑ Verster JC, Veldhuijzen DS, Volkerts ER (August 2004). "Residual effects of sleep medication on driving ability". Sleep Medicine Reviews. 8 (4): 309–25. doi:10.1016/j.smrv.2004.02.001. hdl: 1874/11902 . PMID   15233958. S2CID   22856696.
  16. ↑ Barbera J, Shapiro C (2005). "Benefit-risk assessment of zaleplon in the treatment of insomnia". Drug Safety. 28 (4): 301–18. doi:10.2165/00002018-200528040-00003. PMID   15783240. S2CID   24222535.
  17. ↑ Fick D, Semla T, Beizer J, Brandt N, Dombrowski R, DuBeau CE, et al. (American Geriatrics Society 2012 Beers Criteria Update Expert Panel) (April 2012). "American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults". Journal of the American Geriatrics Society. 60 (4): 616–31. doi:10.1111/j.1532-5415.2012.03923.x. PMC   3571677 . PMID   22376048.
  18. ↑ Antai-Otong D (August 2006). "The art of prescribing. Risks and benefits of non-benzodiazepine receptor agonists in the treatment of acute primary insomnia in older adults". Perspectives in Psychiatric Care. 42 (3): 196–200. doi: 10.1111/j.1744-6163.2006.00070.x . PMID   16916422.
  19. ↑ Bain KT (June 2006). "Management of chronic insomnia in elderly persons". The American Journal of Geriatric Pharmacotherapy. 4 (2): 168–92. doi:10.1016/j.amjopharm.2006.06.006. PMID   16860264.
  20. ↑ Wagner J, Wagner ML, Hening WA (June 1998). "Beyond benzodiazepines: alternative pharmacologic agents for the treatment of insomnia". The Annals of Pharmacotherapy. 32 (6): 680–91. doi:10.1345/aph.17111. PMID   9640488. S2CID   34250754.
  21. ↑ Menzin J, Lang KM, Levy P, Levy E (January 2001). "A general model of the effects of sleep medications on the risk and cost of motor vehicle accidents and its application to France". PharmacoEconomics. 19 (1): 69–78. doi:10.2165/00019053-200119010-00005. PMID   11252547. S2CID   45013069.
  22. ↑ Vermeeren A, Riedel WJ, van Boxtel MP, Darwish M, Paty I, Patat A (March 2002). "Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol". Sleep. 25 (2): 224–31. PMID   11905433.
  23. ↑ Kripke DF (February 2016). "Mortality Risk of Hypnotics: Strengths and Limits of Evidence". Drug Safety. 39 (2): 93–107. doi: 10.1007/s40264-015-0362-0 . PMID   26563222. S2CID   7946506.
  24. ↑ Lader MH (January 2001). "Implications of hypnotic flexibility on patterns of clinical use". International Journal of Clinical Practice. Supplement (116): 14–9. PMID   11219327.
  25. 1 2 Wang JS, DeVane CL (2003). "Pharmacokinetics and drug interactions of the sedative hypnotics" (PDF). Psychopharmacology Bulletin. 37 (1): 10–29. doi:10.1007/BF01990373. PMID   14561946. S2CID   1543185. Archived from the original (PDF) on 9 July 2007. Retrieved 28 December 2008.
  26. ↑ Noguchi H, Kitazumi K, Mori M, Shiba T (January 2002). "Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic". European Journal of Pharmacology. 434 (1–2): 21–28. doi:10.1016/S0014-2999(01)01502-3. PMID   11755161. Binding assays show no binding (IsC50 > 10,000 micromolar) with regards to the 5HT1, 5HT1A, 5-HT2A, 5-HT3, D1, D2, alpha-1 adrenoceptor, alpha-2 adrenoceptor, or M1 receptors.
  27. ↑ Patat A, Paty I, Hindmarch I (July 2001). "Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent". Human Psychopharmacology. 16 (5): 369–392. doi:10.1002/hup.310. PMID   12404558.
  28. ↑ Dämgen K, Lüddens H (1999). "Zaleplon displays a selectivity to recombinant GABAA receptors different from zolipdem, zopiclone and benzodiazepines". Neuroscience Research Communications. 25 (3): 139–148. doi:10.1002/(SICI)1520-6769(199911/12)25:3<139::AID-NRC3>3.0.CO;2-W. ISSN   1520-6769.
  29. ↑ Zeilhofer HU, Witschi R, Hösl K (May 2009). "Subtype-selective GABAA receptor mimetics--novel antihyperalgesic agents?". Journal of Molecular Medicine. 87 (5): 465–469. doi:10.1007/s00109-009-0454-3. PMID   19259638.
  30. ↑ Noguchi H, Kitazumi K, Mori M, Shiba T (January 2002). "Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic". European Journal of Pharmacology. 434 (1–2): 21–28. doi:10.1016/S0014-2999(01)01502-3. PMID   11755161.
  31. ↑ Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T (July 2004). "Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis". Human Psychopharmacology. 19 (5): 305–22. doi:10.1002/hup.594. PMID   15252823. S2CID   10888200.
  32. ↑ Noguchi H, Kitazumi K, Mori M, Shiba T (March 2004). "Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats". Journal of Pharmacological Sciences. 94 (3): 246–51. doi: 10.1254/jphs.94.246 . PMID   15037809.
  33. ↑ Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, et al. (April 2006). "Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors". The Journal of Pharmacology and Experimental Therapeutics. 317 (1): 369–77. doi:10.1124/jpet.105.096701. PMID   16399882. S2CID   46510829.
  34. ↑ Herman JH, Sheldon SH (January 2005). "Chapter 28 - Pharmacology of Sleep Disorders in Children". In Sheldon SH, Ferber R, Kryger MH (eds.). Principles and Practice of Pediatric Sleep Medicine. Philadelphia: W.B. Saunders. pp. 327–338. doi:10.1016/b978-0-7216-9458-0.50033-7. ISBN   978-0-7216-9458-0.
  35. ↑ Patat A, Paty I, Hindmarch I (July 2001). "Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent". Human Psychopharmacology. 16 (5): 369–392. doi:10.1002/hup.310. PMID   12404558. S2CID   21096374.
  36. ↑ Rowlett JK, Spealman RD, Lelas S, Cook JM, Yin W (January 2003). "Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors". Psychopharmacology. 165 (3): 209–215. doi:10.1007/s00213-002-1275-z. PMID   12420154. S2CID   37632215.
  37. ↑ "Zaleplon". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Retrieved 10 June 2018.
  38. ↑ US 4626538,Dusza JP, Tomcufcik AS, Albright JD,"[7-(3-disubstituted amino)phenyl]pyrazolo[1,5-a]pyrimidines",issued 2 December 1986, assigned to American Cyanamid Coand King Pharmaceuticals Research and Development Inc.
  39. ↑ Huang X, Li Y, You Q (May 2002). "Synthesis of Zaleplon". China Pharmacist. Archived from the original on 4 March 2016.
  40. ↑ Banasik M, Komura H, Shimoyama M, Ueda K (January 1992). "Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase". The Journal of Biological Chemistry. 267 (3): 1569–1575. doi: 10.1016/S0021-9258(18)45983-2 . PMID   1530940.
  41. ↑ Dehmel F, Weinbrenner S, Julius H, Ciossek T, Maier T, Stengel T, et al. (July 2008). "Trithiocarbonates as a novel class of HDAC inhibitors: SAR studies, isoenzyme selectivity, and pharmacological profiles". Journal of Medicinal Chemistry. 51 (13): 3985–4001. doi:10.1021/jm800093c. PMID   18558669.
  42. ↑ Salomon RG, Raychaudhuri SR (1984). "Convenient preparation of N,N-dimethylacetamide dimethyl acetal". The Journal of Organic Chemistry. 49 (19): 3659–3660. doi:10.1021/jo00193a045.
  43. ↑ "Sonata (zaleplon) Capsules". DailyMed. U.S. National Library of Medicine.
  44. ↑ Paparrigopoulos T, Tzavellas E, Karaiskos D, Liappas I (November 2008). "Intranasal zaleplon abuse". The American Journal of Psychiatry. 165 (11): 1489–90. doi:10.1176/appi.ajp.2008.08030452. PMID   18981079. Archived from the original on 5 July 2010. Retrieved 5 April 2011.
  45. ↑ Rush CR, Frey JM, Griffiths RR (July 1999). "Zaleplon and triazolam in humans: acute behavioral effects and abuse potential". Psychopharmacology. 145 (1): 39–51. doi:10.1007/s002130051030. PMID   10445371. S2CID   12061258.
  46. ↑ Ator NA (December 2000). "Zaleplon and triazolam: drug discrimination, plasma levels, and self-administration in baboons". Drug and Alcohol Dependence. 61 (1): 55–68. doi:10.1016/S0376-8716(00)00123-X. PMID   11064184.
  47. 1 2 "Zaleplon". Medication Database. Aviation Medicine Advisory Service (AMAS).
  48. 1 2 Caldwell JA, Caldwell JL (July 2005). "Fatigue in military aviation: an overview of US military-approved pharmacological countermeasures" (pdf). Aviation, Space, and Environmental Medicine. 76 (7 Suppl): C39-51. PMID   16018329.
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