Zaleplon

Effects

Overview

Sedative-Hypnotic of the nonbenzodiazepine from the Pyrazolopyramide class. It is used mostly for short term insomnia. TS

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. It was developed by King Pharmaceuticals and approved for medical use in the United States in 1999.[1][2] WP

History

Legal status

Pharmacology

Mechanism of action

Zaleplon is a high-selectivity, 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. 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.[3–6] WP

Unlike nonselective benzodiazepine drugs and zopiclone, which distort the sleep pattern, zaleplon appears to induce sleep without disrupting the normal sleep architecture.[3] WP

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.[7] WP

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. In contrast to non-selective benzodiazepine drugs and zopiclone, zaleplon does not increase power in the β-frequency band.[8][9][10] WP

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.[4][11] WP

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. All of these metabolites are inactive. When taken orally, zaleplon reaches maximum concentration in about 45 minutes.[12][13] WP

Chemistry

Formula

C17H15N5O PC

CAS number

151319-34-5 PC

Molar mass (g/mol)

305.33 PC

IUPAC name (computed by PubChem)

N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-N-ethylacetamide PC

SMILES

CCN(C1=CC=CC(=C1)C2=CC=NC3=C(C=NN23)C#N)C(=O)C PC

InChIKey

HUNXMJYCHXQEGX-UHFFFAOYSA-N PC

PubChem CID

5719

Pop culture

No references added yet.

References

1. Journal / agency Elie R, Rüther E, Farr I, Emilien G, Salinas E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group. The Journal of Clinical Psychiatry. August 1999. doi:10.4088/JCP.v60n0806 · PMID 10485636
2. Journal / agency Sonata (zaleplon) Capsules CIV
3. Journal / agency Noguchi H, Kitazumi K, Mori M, Shiba T. Binding and neuropharmacological profile of zaleplon, a novel nonbenzodiazepine sedative/hypnotic. European Journal of Pharmacology. January 2002. doi:10.1016/S0014-2999(01)01502-3 · PMID 11755161
4. Journal / agency Patat A, Paty I, Hindmarch I. Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Human Psychopharmacology. July 2001. doi:10.1002/hup.310 · PMID 12404558
5. Journal / agency Dämgen K, Lüddens H. Zaleplon displays a selectivity to recombinant GABAA receptors different from zolipdem, zopiclone and benzodiazepines. Neuroscience Research Communications. 1999. doi:10.1002/(SICI)1520-6769(199911/12)25:3<139::AID-NRC3>3.0.CO;2-W
6. Journal / agency Zeilhofer HU, Witschi R, Hösl K. Subtype-selective GABAA receptor mimetics--novel antihyperalgesic agents?. Journal of Molecular Medicine. May 2009. doi:10.1007/s00109-009-0454-3 · PMID 19259638
7. Journal / agency Dündar Y, Dodd S, Strobl J, Boland A, Dickson R, Walley T. Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis. Human Psychopharmacology. July 2004. doi:10.1002/hup.594 · PMID 15252823
8. Journal / agency Noguchi H, Kitazumi K, Mori M, Shiba T. Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. Journal of Pharmacological Sciences. March 2004. doi:10.1254/jphs.94.246 · PMID 15037809
9. Journal / agency Petroski RE, Pomeroy JE, Das R, Bowman H, Yang W, Chen AP, Foster AC. Indiplon is a high-affinity positive allosteric modulator with selectivity for alpha1 subunit-containing GABAA receptors. The Journal of Pharmacology and Experimental Therapeutics. April 2006. doi:10.1124/jpet.105.096701 · PMID 16399882
10. Journal / agency Herman JH, Sheldon SH. Principles and Practice of Pediatric Sleep Medicine. January 2005. doi:10.1016/b978-0-7216-9458-0.50033-7
11. Journal / agency Rowlett JK, Spealman RD, Lelas S, Cook JM, Yin W. Discriminative stimulus effects of zolpidem in squirrel monkeys: role of GABA(A)/alpha1 receptors. Psychopharmacology. January 2003. doi:10.1007/s00213-002-1275-z · PMID 12420154
12. Journal / agency 20859 S009, 011 FDA Approved Labeling Text 12.10.07
13. Journal / agency Rosen AS, Fournié P, Darwish M, Danjou P, Troy SM. Zaleplon pharmacokinetics and absolute bioavailability. Biopharmaceutics & Drug Disposition. April 1999. doi:10.1002/(sici)1099-081x(199904)20:3<171::aid-bdd169>3.0.co;2-k · PMID 10211871

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