Tmic
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Record Information
Version2.0
Creation Date2009-07-15 20:46:17 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2673
Identification
Common NameZaleplon
ClassSmall Molecule
DescriptionZaleplon 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.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Anxiolytic
  • Drug
  • Hypnotic and Sedative
  • Metabolite
  • Nitrile
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
3'-(3-Cyanopyrazolo(1,5-a)pyrimidin-7-yl)-N-ethylacetanilide
DEA No. 2781
Sonata
Zalaplon
Chemical FormulaC17H15N5O
Average Molecular Mass305.334 g/mol
Monoisotopic Mass305.128 g/mol
CAS Registry Number151319-34-5
IUPAC NameN-(3-{3-cyanopyrazolo[1,5-a]pyrimidin-7-yl}phenyl)-N-ethylacetamide
Traditional Namezaleplon
SMILESCCN(C(C)=O)C1=CC=CC(=C1)C1=CC=NC2=C(C=NN12)C#N
InChI IdentifierInChI=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
InChI KeyInChIKey=HUNXMJYCHXQEGX-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative Parents
Substituents
  • 4-phenylpyrimidine
  • 5-phenylpyrimidine
  • Acetanilide
  • Pyrazolo[1,5-a]pyrimidine
  • Anilide
  • Pyrazolopyrimidine
  • Monocyclic benzene moiety
  • Benzenoid
  • Azole
  • Heteroaromatic compound
  • Acetamide
  • Tertiary carboxylic acid amide
  • Pyrazole
  • Carboxamide group
  • Carboxylic acid derivative
  • Carbonitrile
  • Nitrile
  • Azacycle
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organic oxide
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite to off-white powder (RxList, A308).
Experimental Properties
PropertyValue
Melting Point157-159°C
Boiling PointNot Available
Solubility4.03e-02 g/L
LogP0.9
Predicted Properties
PropertyValueSource
Water Solubility0.04 g/LALOGPS
logP2ALOGPS
logP1.53ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)0.3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area74.29 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity97.24 m³·mol⁻¹ChemAxon
Polarizability32.09 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002o-3190000000-e824b41dc4a274647c52View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-0179000000-1ba269c717f4cb21ab11View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0049000000-5aaa826ffa805612f3d8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0bvr-0093000000-ee7356e7d1d88937a5a1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uy3-9070000000-ba55a55873577a61559bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0039000000-f5fc7839e64ab7770cbdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0imi-1192000000-a401fb58f718b462f3e8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01qc-2090000000-3a6f247edccc09a27d47View in MoNA
MSMass Spectrum (Electron Ionization)splash10-01ot-3391000000-78a75199aa0ab8c426beView in MoNA
Toxicity Profile
Route of ExposureIngestion (RxList, A308); inhalation (RxList, A308); dermal (RxList, A308); eye contact (RxList, A308). Absorption Zaleplon is rapidly and almost completely absorbed following oral administration.
Mechanism of ToxicityZaleplon 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. Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (11)
MetabolismZaleplon is primarily metabolized by aldehyde oxidase. Zaleplon is rapidly and almost completely absorbed following oral administration. After oral administration, zaleplon is extensively metabolized, with less than 1% of the dose excreted unchanged in urine. Zaleplon is primarily metabolized by aldehyde oxidase to form 5-oxo-zaleplon. Zaleplon is metabolized to a lesser extent by cytochrome P450 (CYP) 3A4 to form desethylzaleplon, which is quickly converted, presumably by aldehyde oxidase, to 5-oxo-desethylzaleplon. These oxidative metabolites are then converted to glucuronides and eliminated in urine. All of zaleplon's metabolites are pharmacologically inactive (RxList, A308). 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of short-term treatment of insomnia in adults (1).
Minimum Risk LevelNot Available
Health EffectsAngina pectoris, bundle branch block, hypertension, hypotension, palpitation, syncope, melena, mouth ulceration, rectal hemorrhage, stomatitis, dysphagia, enteritis, gum hemorrhage, diabetes mellitus, goiter, hypothyroidism, arthrosis, bursitis, hyperesthesia, hyperkinesia, hypotonia, incoordination, insomnia, libido decreased, neuralgia, nystagmus, dry skin, eczema, maculopapular rash, skin hypertrophy, dysuria, hematuria, impotence, kidney calculus, kidney pain, urinary retention, and vaginal hemorrhage (RxList, A308). They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive. May cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSide effects include abdominal pain, amnesia, dizziness, drowsiness, eye pain, headache, memory loss, menstrual pain, nausea, sleepiness, tingling, weakness
TreatmentGeneral symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. (10)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00962
HMDB IDHMDB15097
PubChem Compound ID5719
ChEMBL IDCHEMBL1521
ChemSpider ID5517
KEGG IDC07484
UniProt IDNot Available
OMIM ID
ChEBI ID10102
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZaleplon
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkZaleplon
References
Synthesis Reference

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

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  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. [15037809 ]
  3. 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. [15252823 ]
  4. Ramakrishnan K, Scheid DC: Treatment options for insomnia. Am Fam Physician. 2007 Aug 15;76(4):517-26. [17853625 ]
  5. Barbera J, Shapiro C: Benefit-risk assessment of zaleplon in the treatment of insomnia. Drug Saf. 2005;28(4):301-18. [15783240 ]
  6. Dooley M, Plosker GL: Zaleplon: a review of its use in the treatment of insomnia. Drugs. 2000 Aug;60(2):413-45. [10983740 ]
  7. 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. [10804040 ]
  8. Patat A, Paty I, Hindmarch I: Pharmacodynamic profile of Zaleplon, a new non-benzodiazepine hypnotic agent. Hum Psychopharmacol. 2001 Jul;16(5):369-392. [12404558 ]
  9. Drugs.com [Link]
  10. RxList: The Internet Drug Index (2009). [Link]
  11. Wikipedia. Cyanide poisoning. Last Updated 30 March 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
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. [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. [17016423 ]
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 lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
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. [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. [17016423 ]