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Identification
Name Zaleplon
Accession Number DB00962 (APRD00411)
Type small molecule
Groups illicit, approved
Description

Zaleplon is a sedative/hypnotic, mainly used for insomnia. It is known as a nonbenzodiazepine hypnotic. Zaleplon interacts with the GABA receptor complex and shares some of the pharmacological properties of the benzodiazepines. Zaleplon is a schedule IV drug in the United States.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
DEA No. 2781
Salts Not Available
Brand names
Name Company
Sonata
Zalaplon
Brand mixtures Not Available
Categories
  • Hypnotics and Sedatives
  • Anticonvulsants
  • Anxiolytics sedatives and hypnotics
CAS number 151319-34-5
Weight Average: 305.3339
Monoisotopic: 305.127660127
Chemical Formula C17H15N5O
InChI Key InChIKey=HUNXMJYCHXQEGX-UHFFFAOYSA-N
InChI
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
Plain Text
IUPAC Name
N-(3-{3-cyanopyrazolo[1,5-a]pyrimidin-7-yl}phenyl)-N-ethylacetamide
SMILES
CCN(C(C)=O)C1=CC=CC(=C1)C1=CC=NC2=C(C=NN12)C#N
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Acetanilides
  • Pyrazolopyrimidines
Substructures
  • Pyrazoles
  • Amino Ketones
  • Nitriles and Derivatives
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Acetanilides
  • Pyrimidines and Derivatives
  • Cyanides
  • Pyrazolopyrimidines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Imines
  • Cyanamides
  • Anilines
Pharmacology
Indication For the treatment of short-term treatment of insomnia in adults.
Pharmacodynamics Zaleplon is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zaleplon is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zaleplon also binds selectively to the CNS GABAA-receptor chloride ionophore complex at benzodiazepine(BZ) omega-1 (BZ1, ο1) receptors.
Mechanism of action Zaleplon exerts its action through subunit modulation of the GABABZ receptor chloride channel macromolecular complex. Zaleplon also binds selectively to the brain omega-1 receptor located on the alpha subunit of the GABA-A/chloride ion channel receptor complex and potentiates t-butyl-bicyclophosphorothionate (TBPS) binding.
Absorption Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.
Volume of distribution
  • 1.4 L/kg
Protein binding Approximately 60% (in vitro plasma protein binding).
Metabolism Zaleplon is primarily metabolized by aldehyde oxidase.
Route of elimination Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. After oral administration, zaleplon is extensively metabolized, with less than 1% of the dose excreted unchanged in urine. Renal excretion of unchanged zaleplon accounts for less than 1% of the administered dose.
Half life Approximately 1 hour
Clearance
  • 1 L/h/kg
Toxicity Side effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals research and development inc sub king pharmaceuticals inc
  • Aurobindo pharma ltd
  • Cipla ltd
  • Mylan pharmaceuticals inc
  • Orchid healthcare div orchid chemicals and pharmaceuticals ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Unichem laboratories ltd
  • Upsher smith laboratories inc
  • West ward pharmaceutical corp
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Sonata 10 mg capsule 6.83 USD capsule
Sonata 5 mg capsule 5.26 USD capsule
Zaleplon 5 mg capsule 2.13 USD capsule
Zaleplon 10 mg capsule 2.09 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 157-159 °C Not Available
logP 0.9 Not Available
Predicted Properties
Property Value Source
water solubility 4.03e-02 g/l ALOGPS
logP 2 ALOGPS
logP 1.53 ChemAxon
logS -3.9 ALOGPS
pKa (strongest basic) 0.3 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 74.29 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 97.24 ChemAxon
polarizability 32.09 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Dundar 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. Hum Psychopharmacol. 2004 Jul;19(5):305-22. Pubmed
  2. Noguchi H, Kitazumi K, Mori M, Shiba T: Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats. J Pharmacol Sci. 2004 Mar;94(3):246-51. Pubmed
  3. Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Physician. 2007 Aug 15;76(4):517-26. Pubmed
  4. Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. Pubmed
  5. Dooley M, Plosker GL: Zaleplon: a review of its use in the treatment of insomnia. Drugs. 2000 Aug;60(2):413-45. Pubmed
  6. Holm KJ, Goa KL: Zolpidem: an update of its pharmacology, therapeutic efficacy and tolerability in the treatment of insomnia. Drugs. 2000 Apr;59(4):865-89. Pubmed
  7. Patat A, Paty I, Hindmarch I: Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol. 2001 Jul;16(5):369-392. Pubmed
External Links
Resource Link
KEGG Drug D00530 Link_out
KEGG Compound C07484 Link_out
PubChem Compound 5719 Link_out
PubChem Substance 46508267 Link_out
ChemSpider 5517 Link_out
ChEBI 10102 Link_out
ChEMBL 10102 Link_out
Therapeutic Targets Database DAP000266 Link_out
PharmGKB PA451952 Link_out
Drug Product Database 2242219 Link_out
RxList http://www.rxlist.com/cgi/generic3/zaleplon.htm Link_out
Drugs.com http://www.drugs.com/cdi/zaleplon.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/son1537.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Zaleplon Link_out
ATC Codes
  • N05CF03
AHFS Codes
  • 28:24.92
PDB Entries Not Available
FDA label show (66.1 KB)
MSDS show (57.6 KB)
Interactions
Drug Interactions
Drug Interaction
Cimetidine Cimetidine may increase the serum concentration of zaleplon by decreasing its metabolism. Reduce the initial dose of zaleplon to 5 mg in patients receiving cimetidine.
Methotrimeprazine Additive CNS depressant effects may occur. A dose reduction of zaleplon may be required. Monitor for increased CNS depression during concomitant therapy.
Rifampin Rifampin decreases the effect of zaleplon
Triprolidine The CNS depressants, Triprolidine and Zaleplon, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food Interactions Not Available
Targets

1. Gamma-aminobutyric-acid receptor subunit alpha-1

Pharmacological action: yes
Actions: potentiator

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel

Organism class: human
UniProt ID: P14867 Link_out
Gene: GABRA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Patat A, Paty I, Hindmarch I: Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol. 2001 Jul;16(5):369-392. Pubmed
  4. Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. Pubmed
  5. Sanger DJ, Griebel G, Perrault G, Claustre Y, Schoemaker H: Discriminative stimulus effects of drugs acting at GABA receptors: differential profiles and receptor selectivity. Pharmacol Biochem Behav. 1999 Oct;64(2):269-73. Pubmed
  6. Terzano MG, Rossi M, Palomba V, Smerieri A, Parrino L: New drugs for insomnia: comparative tolerability of zopiclone, zolpidem and zaleplon. Drug Saf. 2003;26(4):261-82. Pubmed

2. Translocator protein

Pharmacological action: yes
Actions: other

Responsible for the manifestation of peripheral-type benzodiazepine recognition sites and is most likely to comprise binding domains for benzodiazepines and isoquinoline carboxamides. May play a role in the transport of porphyrins and heme

Organism class: human
UniProt ID: P30536 Link_out
Gene: TSPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Williams DA, Foye WO, Lemke TL. Foye’s principles of medicinal chemistry. Lippincott Williams & Wilkins; 2002.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Aldehyde oxidase

Actions: substrate

An aldehyde + H(2)O + O(2) = a carboxylic acid + H(2)O(2)

UniProt ID: Q06278 Link_out
Gene: AOX1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lake BG, Ball SE, Kao J, Renwick AB, Price RJ, Scatina JA: Metabolism of zaleplon by human liver: evidence for involvement of aldehyde oxidase. Xenobiotica. 2002 Oct;32(10):835-47. Pubmed
  2. Obach RS: Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos. 2004 Jan;32(1):89-97. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19