Identification

Name
Zaleplon
Accession Number
DB00962  (APRD00411)
Type
Small Molecule
Groups
Approved, 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
Synonyms
  • 3'-(3-Cyanopyrazolo(1,5-a)pyrimidin-7-yl)-N-ethylacetanilide
External IDs
CL 284,846 / CL-284846 / DEA No. 2781 / L846 / LJC 10846 / LJC-10846 / SKP-1041 / ZAL-846
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SonataCapsule5 mg/1OralPfizer Laboratories Div Pfizer Inc.1999-08-13Not applicableUs
SonataCapsule10 mg/1OralPhysicians Total Care, Inc.2004-04-01Not applicableUs
SonataCapsule10 mg/1OralPfizer Laboratories Div Pfizer Inc.1999-08-13Not applicableUs
SonataCapsule5 mg/1OralPhysicians Total Care, Inc.2007-09-05Not applicableUs
StarnocCapsule10 mgOralPfizerNot applicableNot applicableCanada
StarnocCapsule5 mgOralServier2000-06-272007-09-27Canada
StarnocCapsule5 mgOralPfizerNot applicableNot applicableCanada
StarnocCapsule10 mgOralServier2000-06-272007-09-27Canada
ZaleplonCapsule5 mg/1Oralbryant ranch prepack2008-05-01Not applicableUs
ZaleplonCapsule10 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2011-12-05Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ZaleplonCapsule10 mg/1Oralbryant ranch prepack2009-05-05Not applicableUs
ZaleplonCapsule5 mg/1OralUnichem Pharmaceuticals (USA), Inc.2009-05-05Not applicableUs
ZaleplonCapsule10 mg/1OralAscend Laboratories, LLC2010-12-15Not applicableUs
ZaleplonCapsule10 mg/1OralAidarex Pharmaceuticals LLC2009-05-05Not applicableUs
ZaleplonCapsule5 mg/1OralWest-Ward Pharmaceuticals Corp.2008-06-06Not applicableUs
ZaleplonCapsule10 mg/1OralRising Health, Llc2008-06-06Not applicableUs
ZaleplonCapsule5 mg/1OralWest Ward Pharmaceutical2008-12-012010-12-01Us
ZaleplonCapsule5 mg/1OralGreenstone, Llc2008-06-062013-03-31Us
ZaleplonCapsule10 mg/1OralA S Medication Solutions2008-06-06Not applicableUs54569 611820180907 15195 1k95e52
ZaleplonCapsule5 mg/1OralMylan Pharmaceuticals2008-06-062016-06-30Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
SonataZaleplon (10 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
SonataZaleplon (5 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
SonataZaleplon (10 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
SonataZaleplon (5 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
SonataZaleplon (10 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
SonataZaleplon (5 mg)CapsuleOralMeda Ab1999-03-122015-10-21Eu
International/Other Brands
Zalaplon
Categories
UNII
S62U433RMH
CAS number
151319-34-5
Weight
Average: 305.3339
Monoisotopic: 305.127660127
Chemical Formula
C17H15N5O
InChI Key
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

Pharmacology

Indication

For the treatment of short-term treatment of insomnia in adults.

Associated Conditions
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.

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Human
ATranslocator protein
other
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Zaleplon.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Zaleplon.
16-BromoepiandrosteroneThe metabolism of 16-Bromoepiandrosterone can be decreased when combined with Zaleplon.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Zaleplon is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineZaleplon may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Zaleplon is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Zaleplon.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Zaleplon is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Zaleplon.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Zaleplon is combined with 4-Methoxyamphetamine.
Food Interactions
Not 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 References
  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:15252823]
  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:15037809]
  3. Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Physician. 2007 Aug 15;76(4):517-26. [PubMed:17853625]
  4. Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. [PubMed:15783240]
  5. Dooley M, Plosker GL: Zaleplon: a review of its use in the treatment of insomnia. Drugs. 2000 Aug;60(2):413-45. [PubMed:10983740]
  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:10804040]
  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:12404558]
External Links
Human Metabolome Database
HMDB0015097
KEGG Drug
D00530
KEGG Compound
C07484
PubChem Compound
5719
PubChem Substance
46508267
ChemSpider
5517
BindingDB
86521
ChEBI
10102
ChEMBL
CHEMBL1521
Therapeutic Targets Database
DAP000266
PharmGKB
PA451952
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Zaleplon
ATC Codes
N05CF03 — Zaleplon
AHFS Codes
  • 28:24.92 — Miscellaneous Anxiolytics Sedatives and Hypnotics
FDA label
Download (66.1 KB)
MSDS
Download (57.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
2CompletedTreatmentClinical Depression / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2CompletedTreatmentPrimary Insomnia / Sleep Disorder1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
4CompletedBasic ScienceMemory / Sleep1
4CompletedSupportive CareCognition / Pharmacologic Actions / Sleep1
Not AvailableCompletedTreatmentShort Term Treatment of Insomnia2
Not AvailableRecruitingNot AvailableSleep1

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
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Cipla Ltd.
  • Corepharma LLC
  • DAVA Pharmaceuticals
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Greenstone LLC
  • Innoviant Pharmacy Inc.
  • King Pharmaceuticals Inc.
  • Mylan
  • Northstar Rx LLC
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Roxane Labs
  • Teva Pharmaceutical Industries Ltd.
  • Unichem Laboratories Ltd.
  • USL Pharma Inc.
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral10 mg
CapsuleOral5 mg
CapsuleOral10 mg/1
CapsuleOral5 mg/1
Capsule, gelatin coatedOral10 mg/1
Capsule, gelatin coatedOral5 mg/1
Prices
Unit descriptionCostUnit
Sonata 10 mg capsule6.83USD capsule
Sonata 5 mg capsule5.26USD capsule
Zaleplon 5 mg capsule2.13USD capsule
Zaleplon 10 mg capsule2.09USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)157-159 °CNot Available
logP0.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0403 mg/mLALOGPS
logP2ALOGPS
logP1.53ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)0.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area74.29 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity97.24 m3·mol-1ChemAxon
Polarizability32.09 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9751
Caco-2 permeable+0.5973
P-glycoprotein substrateNon-substrate0.6094
P-glycoprotein inhibitor INon-inhibitor0.5232
P-glycoprotein inhibitor IIInhibitor0.8239
Renal organic cation transporterNon-inhibitor0.745
CYP450 2C9 substrateNon-substrate0.8607
CYP450 2D6 substrateNon-substrate0.8551
CYP450 3A4 substrateSubstrate0.6341
CYP450 1A2 substrateNon-inhibitor0.5
CYP450 2C9 inhibitorInhibitor0.5986
CYP450 2D6 inhibitorNon-inhibitor0.9507
CYP450 2C19 inhibitorNon-inhibitor0.5238
CYP450 3A4 inhibitorNon-inhibitor0.8396
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7673
Ames testNon AMES toxic0.5372
CarcinogenicityNon-carcinogens0.6481
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6277 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9806
hERG inhibition (predictor II)Non-inhibitor0.8931
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-01ot-3391000000-78a75199aa0ab8c426be
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0179000000-1ba269c717f4cb21ab11

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazines
Sub Class
Pyrimidines and pyrimidine derivatives
Direct Parent
Phenylpyrimidines
Alternative Parents
Acetanilides / Pyrazolo[1,5-a]pyrimidines / Tertiary carboxylic acid amides / Pyrazoles / Heteroaromatic compounds / Acetamides / Nitriles / Azacyclic compounds / Organopnictogen compounds / Organic oxides
show 2 more
Substituents
4-phenylpyrimidine / 5-phenylpyrimidine / Acetanilide / Pyrazolo[1,5-a]pyrimidine / Anilide / Pyrazolopyrimidine / Monocyclic benzene moiety / Benzenoid / Azole / Heteroaromatic compound
show 17 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
nitrile, pyrazolopyrimidine (CHEBI:10102)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
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:17139284]
  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:17016423]
  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:12404558]
  4. Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. [PubMed:15783240]
  5. Sanger DJ, Griebel G, Perrault G, Claustre Y, Schoemaker H: Discriminative stimulus effects of drugs acting at GABA(A) receptors: differential profiles and receptor selectivity. Pharmacol Biochem Behav. 1999 Oct;64(2):269-73. [PubMed:10515302]
  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:12608888]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Other
General Function
Cholesterol binding
Specific Function
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in l...
Gene Name
TSPO
Uniprot ID
P30536
Uniprot Name
Translocator protein
Molecular Weight
18827.81 Da
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:17139284]
  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:17016423]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Foye, William O.;Williams, David A.;Lemke, Thomas L. (2002). Foye's Principles of Medicinal Chemistry (5th ed.). Lippincott Williams & Wilkins. [ISBN:0683307371]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xanthine dehydrogenase activity
Specific Function
Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal...
Gene Name
AOX1
Uniprot ID
Q06278
Uniprot Name
Aldehyde oxidase
Molecular Weight
147916.735 Da
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:12419014]
  2. Obach RS: Potent inhibition of human liver aldehyde oxidase by raloxifene. Drug Metab Dispos. 2004 Jan;32(1):89-97. [PubMed:14709625]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:32