Zaleplon

Source: Wikipedia, the free encyclopedia.
Zaleplon
Clinical data
By mouth
Drug classPyrazolopyrimidine
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability30% (oral)[3]
MetabolismLiver aldehyde oxidase (91%), CYP3A4 (9%)[4]
Elimination half-life1 hr[3]
ExcretionKidney
Identifiers
  • N-(3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl)phenyl)-N-ethylacetamide
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 checkY
  • Key:HUNXMJYCHXQEGX-UHFFFAOYSA-N checkY
  (verify)

Zaleplon, sold under the brand name Sonata among others, is a

Z-drug of the pyrazolopyrimidine class.[5] It was developed by King Pharmaceuticals and approved for medical use in the United States in 1999.[6]

Medical uses

Zaleplon is slightly effective in treating insomnia,[7] 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.[8][9][10] 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.[8] However, zaleplon has not been empirically shown to increase total sleep time.[10][8]

Zaleplon does not significantly affect driving performance the morning following bedtime administration or 4 hours after middle-of-the-night administration.

benzodiazepines with fewer adverse effects.[12]

Special populations

Zaleplon is not recommended for chronic use in the elderly.[13] 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.[14]

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.[15]

Adverse effects

The adverse effects of zaleplon are similar to the adverse effects of benzodiazepines, although with less next-day sedation,

hypnotics currently on the market.[17][18]

Sleeping pills, including zaleplon, have been associated with an increased risk of death.[19]

Some evidence suggests zaleplon is not as chemically reinforcing and exhibits far fewer

Z-drugs.[20]

Interactions

The

liver enzyme is a minor metabolic pathway for zaleplon, normally metabolizing about 9% of the drug.[4] 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.[4]

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.[21] Diphenhydramine, a weak inhibitor of aldehyde oxidase, has not been found to affect the pharmacokinetics of zaleplon.[21]

Pharmacology

Mechanism of action

Zaleplon is a high-selectivity,

sleep architecture.[25]

A

rebound insomnia, and daytime alertness.[26]

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[27][28]

Pharmacokinetics

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.[4][3] All of these metabolites are inactive.[3] When taken orally, zaleplon reaches maximum concentration in about 45 minutes.[3]

Chemistry

Zaleplon is classified as a pyrazolopyrimidine.[29] 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.[4] It has a constant octanol-water partition coefficient of log P = 1.23 in the pH range between 1 and 7.[4]

Synthesis

Zaleplon synthesis[30][31]

The synthesis starts with the condensation of

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.[35]

Some individuals use a different delivery method than prescribed, such as insufflation, to induce effects faster.[36]

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.[37][38]

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.[39] The substances with the 2nd shortest period, which is of 24 hours, are zolpidem and ramelteon.[39]

Military use

The

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.[40] The other hypnotics used as "no-go pills" are temazepam and zolpidem, which both have longer mandatory recovery periods.[40]

References

  1. FDA
    . Retrieved 22 Oct 2023.
  2. ^ Anvisa (2023-03-31). "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 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  3. ^
    PMID 10211871
    .
  4. ^ a b c d e f "20859 S009, 011 FDA Approved Labeling Text 12.10.07" (PDF). FDA. Retrieved 21 March 2023.
  5. PMID 10485636
    .
  6. ^ "Sonata (zaleplon) Capsules CIV". DailyMed. Retrieved 21 March 2023.
  7. PMID 23248080
    .
  8. ^
    PMID 31855398
    . Retrieved 2020-07-08.
  9. PMID 23616704
    .
  10. ^
    S2CID 195691571
    .
  11. S2CID 22856696
    .
  12. S2CID 24222535
    .
  13. PMID 22376048.{{cite journal}}: CS1 maint: numeric names: authors list (link
    )
  14. PMID 16916422
    .
  15. PMID 16860264
    .
  16. S2CID 34250754
    .
  17. S2CID 45013069
    .
  18. PMID 11905433
    .
  19. S2CID 7946506
    .
  20. PMID 11219327
    .
  21. ^
    S2CID 1543185. Archived from the original
    (PDF) on 2007-07-09. Retrieved 2008-12-28.
  22. PMID 11755161
    .
  23. S2CID 21096374
    .
  24. S2CID 37632215
    .
  25. PMID 11755161
    .
  26. S2CID 10888200
    .
  27. PMID 15037809. Archived from the original
    (pdf) on 2008-12-11. Retrieved 2007-09-26.
  28. S2CID 46510829
    .
  29. ^ "Zaleplon". pubchem.ncbi.nlm.nih.gov. U.S. National Library of Medicine. Retrieved 10 June 2018.
  30. ^ J. P. Dusza et al., U.S. patent 4,626,538 (1986 to Am. Cyanamid).
  31. ^ http://en.cnki.com.cn/Article_en/CJFDTotal-ZYSG200205002.htm 《China Pharmacist》 2002-05 Synthesis of Zaleplon.
  32. PMID 1530940
    .
  33. PMID 18558669
    .
  34. doi:10.1021/jo00193a045
    .
  35. ^ "Sonata®(zaleplon)Capsules".
  36. PMID 18981079. Archived from the original
    on 2010-07-05. Retrieved 2011-04-05.
  37. S2CID 12061258
    .
  38. PMID 11064184
    .
  39. ^ a b "Medication Database – AMAS".
  40. ^
    PMID 16018329
    .
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