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Identification
NameZaleplon
Accession NumberDB00962  (APRD00411)
Typesmall molecule
Groupsapproved, illicit, investigational
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
SynonymsNot Available
SaltsNot Available
Brand names
NameCompany
SonataNot Available
ZalaplonNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number151319-34-5
WeightAverage: 305.3339
Monoisotopic: 305.127660127
Chemical FormulaC17H15N5O
InChI KeyInChIKey=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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassDiazines
SubclassPyrimidines and Pyrimidine Derivatives
Direct parentPhenylpyrimidines
Alternative parentsAnilides; Pyrazolopyrimidines; Tertiary Carboxylic Acid Amides; Pyrazoles; Tertiary Amines; Nitriles; Enolates; Carboxylic Acids; Polyamines
Substituentsacetanilide; pyrazolopyrimidine; benzene; tertiary carboxylic acid amide; azole; pyrazole; carboxamide group; tertiary amine; polyamine; nitrile; enolate; carbonitrile; carboxylic acid derivative; carboxylic acid; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond.
Pharmacology
IndicationFor the treatment of short-term treatment of insomnia in adults.
PharmacodynamicsZaleplon 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 actionZaleplon 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.
AbsorptionAbsorption Zaleplon is rapidly and almost completely absorbed following oral administration.
Volume of distribution
  • 1.4 L/kg
Protein bindingApproximately 60% (in vitro plasma protein binding).
Metabolism

Zaleplon is primarily metabolized by aldehyde oxidase.

SubstrateEnzymesProduct
Zaleplon
desethylzaleplonDetails
Route of eliminationZaleplon 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 lifeApproximately 1 hour
Clearance
  • 1 L/h/kg
ToxicitySide effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9751
Caco-2 permeable + 0.5973
P-glycoprotein substrate Non-substrate 0.6094
P-glycoprotein inhibitor I Non-inhibitor 0.5232
P-glycoprotein inhibitor II Inhibitor 0.8239
Renal organic cation transporter Non-inhibitor 0.745
CYP450 2C9 substrate Non-substrate 0.8607
CYP450 2D6 substrate Non-substrate 0.8551
CYP450 3A4 substrate Substrate 0.6341
CYP450 1A2 substrate Non-inhibitor 0.5
CYP450 2C9 substrate Inhibitor 0.5986
CYP450 2D6 substrate Non-inhibitor 0.9507
CYP450 2C19 substrate Non-inhibitor 0.5238
CYP450 3A4 substrate Non-inhibitor 0.8396
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7673
Ames test Non AMES toxic 0.5372
Carcinogenicity Non-carcinogens 0.6481
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.6277 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9806
hERG inhibition (predictor II) Non-inhibitor 0.8931
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
FormRouteStrength
CapsuleOral
Prices
Unit descriptionCostUnit
Sonata 10 mg capsule6.83USDcapsule
Sonata 5 mg capsule5.26USDcapsule
Zaleplon 5 mg capsule2.13USDcapsule
Zaleplon 10 mg capsule2.09USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point157-159 °CNot Available
logP0.9Not Available
Predicted Properties
PropertyValueSource
water solubility4.03e-02 g/lALOGPS
logP2ALOGPS
logP1.53ChemAxon
logS-3.9ALOGPS
pKa (strongest basic)0.3ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count0ChemAxon
polar surface area74.29ChemAxon
rotatable bond count3ChemAxon
refractivity97.24ChemAxon
polarizability32.09ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Farhan Aslam, “Polymorphs of zaleplon and methods for the preparation thereof.” U.S. Patent US20020072527, issued June 13, 2002.

US20020072527
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
ResourceLink
KEGG DrugD00530
KEGG CompoundC07484
PubChem Compound5719
PubChem Substance46508267
ChemSpider5517
ChEBI10102
ChEMBLCHEMBL1521
Therapeutic Targets DatabaseDAP000266
PharmGKBPA451952
Drug Product Database2242219
RxListhttp://www.rxlist.com/cgi/generic3/zaleplon.htm
Drugs.comhttp://www.drugs.com/cdi/zaleplon.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/son1537.shtml
WikipediaZaleplon
ATC CodesN05CF03
AHFS Codes
  • 28:24.92
PDB EntriesNot Available
FDA labelshow(66.1 KB)
MSDSshow(57.6 KB)
Interactions
Drug Interactions
Drug
CimetidineCimetidine may increase the serum concentration of zaleplon by decreasing its metabolism. Reduce the initial dose of zaleplon to 5 mg in patients receiving cimetidine.
MethotrimeprazineAdditive CNS depressant effects may occur. A dose reduction of zaleplon may be required. Monitor for increased CNS depression during concomitant therapy.
RifampicinRifampin decreases the effect of zaleplon
TriprolidineThe CNS depressants, Triprolidine and Zaleplon, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Food InteractionsNot Available

1. Gamma-aminobutyric acid receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit alpha-1 P14867 Details

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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: other

Components

Name UniProt ID Details
Translocator protein P30536 Details

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

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

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

4. Aldehyde oxidase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Aldehyde oxidase Q06278 Details

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 September 16, 2013 17:12