U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C17H15N5O
Molecular Weight 305.3345
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZALEPLON

SMILES

CCN(C(=O)C)c1cccc(c1)-c2ccnc3c(C#N)cnn23

InChI

InChIKey=HUNXMJYCHXQEGX-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00962

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. 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. Zaleplon is marketed under the brand names Sonata, Starnoc, and Andante.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Sonata

Approved Use

Sonata is indicated for the short-term treatment of insomnia.

Launch Date

9.3441602E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
14.5 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
62 ng/mL
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
26.9 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
86.1 ng × h/mL
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.08 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.05 h
5 mg single, intravenous
dose: 5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZALEPLON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
40%
ZALEPLON plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
75 mg single, oral
Highest studied dose
Dose: 75 mg
Route: oral
Route: single
Dose: 75 mg
Sources: Page: p.41
healthy, 18 - 44
n = 14
Health Status: healthy
Age Group: 18 - 44
Sex: M+F
Population Size: 14
Sources: Page: p.41
200 mg single, oral (min)
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.12
Other AEs: Loss of consciousness...
Other AEs:
Loss of consciousness
Sources: Page: p.12
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Disc. AE: Sleep driving, Suicide...
Other AEs: Abnormal thinking, Abnormal behavior...
AEs leading to
discontinuation/dose reduction:
Sleep driving
Suicide
Anaphylactic reaction (severe)
Anaphylactoid reaction (severe)
Angioedema (grade 3-5)
Other AEs:
Abnormal thinking
Abnormal behavior
Amnesia
Depression worsened
Suicidal tendency
Sources: Page: p.5
AEs

AEs

AESignificanceDosePopulation
Loss of consciousness
200 mg single, oral (min)
Overdose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources: Page: p.12
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.12
Abnormal behavior
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Abnormal thinking
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Amnesia
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Depression worsened
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Suicidal tendency
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Sleep driving Disc. AE
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Suicide Disc. AE
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Angioedema grade 3-5
Disc. AE
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Anaphylactic reaction severe
Disc. AE
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Anaphylactoid reaction severe
Disc. AE
20 mg 1 times / day multiple, oral (max)
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: p.5
unhealthy
Health Status: unhealthy
Condition: Insomnia
Sources: Page: p.5
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
yes
yes
yes (co-administration study)
Comment: Rifampicin is a strong CYP3A4 inducer. Multiple dosing of rifampicin (600 mg qd for 13 days) reduces both Cmax and AUC of zaleplon to 25% of its respective value, caused by a 5 fold increase in zaleplon oral clearance.
Page: 6.0
PubMed

PubMed

TitleDatePubMed
Zaleplon improves sleep quality in maintenance hemodialysis patients.
2003
Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance.
2003 Dec
Changes in GABA(A) receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal.
2003 Dec 17
Preference of insomniac patients between a single dose of zolpidem 10 mg versus zaleplon 10 mg.
2003 Jul
Mixed drug intoxication involving zaleplon ("Sonata").
2003 Jul 8
Ziprasidone metabolism, aldehyde oxidase, and clinical implications.
2003 Jun
Zaleplon and driving impairment.
2003 May
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
Effect of zaleplon, a non-benzodiazepine hypnotic, on melatonin secretion in rabbits.
2003 Oct
Separation and identification of zaleplon metabolites in human urine using capillary electrophoresis with laser-induced fluorescence detection and liquid chromatography-mass spectrometry.
2003 Oct 3
[Drug treatment of sleep disorders in the elderly].
2003 Sep
Pharmacokinetics and drug interactions of the sedative hypnotics.
2003 Winter
The pharmacology and mechanisms of action of new generation, non-benzodiazepine hypnotic agents.
2004
Residual effects of hypnotics: epidemiology and clinical implications.
2004
Effects of zolpidem and zaleplon on sleep, respiratory patterns and performance at a simulated altitude of 4,000 m.
2004
Comparative pharmacokinetics and pharmacodynamics of short-acting hypnosedatives: zaleplon, zolpidem and zopiclone.
2004
"A comparison of the effectiveness of two hypnotic agents for the treatment of insomnia".
2004 Aug
Sleeping pills without regrets. They've long been the risky quick fixes of sleep medicine. Soon some sleeping pills may be sold as long-term solutions.
2004 Aug
Zaleplon overdose associated with sleepwalking and complex behavior.
2004 Aug
Residual effects of sleep medication on driving ability.
2004 Aug
Hypnotic efficacy of zaleplon for daytime sleep in rested individuals.
2004 Aug 1
Perchance, to sleep...and then stay asleep.
2004 Dec
What's wrong with prescribing hypnotics?
2004 Dec
Direct injection, column switching-liquid chromatographic technique for the estimation of rabeprazole in bioequivalence study.
2004 Dec 25
Performance following a sudden awakening from daytime nap induced by zaleplon.
2004 Jan
Potent inhibition of human liver aldehyde oxidase by raloxifene.
2004 Jan
Comparative efficacy of newer hypnotic drugs for the short-term management of insomnia: a systematic review and meta-analysis.
2004 Jul
Validated semiquantitative/quantitative screening of 51 drugs in whole blood as silylated derivatives by gas chromatography-selected ion monitoring mass spectrometry and gas chromatography electron capture detection.
2004 Jul 5
Sleep-inducing pharmaceuticals: a comparison of melatonin, zaleplon, zopiclone, and temazepam.
2004 Jun
Newer hypnotic drugs for the short-term management of insomnia: a systematic review and economic evaluation.
2004 Jun
Electroencephalographic properties of zaleplon, a non-benzodiazepine sedative/hypnotic, in rats.
2004 Mar
An assessment of quality of sleep and the use of drugs with sedating properties in hospitalized adult patients.
2004 Mar 24
Treatment of primary insomnia.
2004 May-Jun
Characterization of the interaction of indiplon, a novel pyrazolopyrimidine sedative-hypnotic, with the GABAA receptor.
2004 Nov
In vivo pharmacological characterization of indiplon, a novel pyrazolopyrimidine sedative-hypnotic.
2004 Nov
Benefit-risk assessment of zaleplon in the treatment of insomnia.
2005
Determination of 14 benzodiazepines and hydroxy metabolites, zaleplon and zolpidem as tert-butyldimethylsilyl derivatives compared with other common silylating reagents in whole blood by gas chromatography-mass spectrometry.
2005 Apr 25
Validated liquid chromatographic ultraviolet method for the quantitation of Etoricoxib in human plasma using liquid-liquid extraction.
2005 Feb 25
Eszopiclone (Lunesta), a new hypnotic.
2005 Feb 28
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid by LC-MS/MS.
2005 Jun 10
Diagnosis and treatment of chronic insomnia: a review.
2005 Mar
A NICE missed opportunity?
2005 Mar
Short-term treatment with hypnotic drugs for insomnia: going beyond the evidence.
2005 Mar
Making decisions in the absence of high quality clinical evidence: we need to bring some science into the judgement.
2005 Mar
NICE review: not nice for patients!
2005 Mar
NICE: The National Institute of Clinical Excellence -- or Eccentricity? Reflections on the Z-drugs as hypnotics.
2005 Mar
Long-term use of sedative hypnotics in older patients with insomnia.
2005 Mar
Contribution of alpha 1GABAA and alpha 5GABAA receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys.
2005 May
The new Z-drugs as sedatives and hypnotics.
2005 May-Jun
Patents

Sample Use Guides

The recommended dose of Sonata (Zaleplon) for most nonelderly adults is 10 mg. For certain low weight individuals, 5 mg may be a sufficient dose. Although the risk of certain adverse events associated with the use of Sonata appears to be dose dependent, the 20 mg dose has been shown to be adequately tolerated and may be considered for the occasional patient who does not benefit from a trial of a lower dose. Doses above 20 mg have not been adequately evaluated and are not recommended. Sonata should be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep.
Route of Administration: Oral
Zaleplon (1x10(-8) to 3x10(-6) M) exhibited marked efficacy in potentiating GABA-evoked Cl  currents in voltage-clamped Xenopus oocytes expressing human a1b2g2 GABAA receptors.
Name Type Language
ZALEPLON
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ZALEPLON CIV
USP-RS  
Common Name English
ZALEPLON [MART.]
Common Name English
ZAL-846
Code English
ZALEPLON [USP MONOGRAPH]
Common Name English
ACETAMIDE, N-(3-(3-CYANOPYRAZOLO(1,5-.ALPHA.)PYRIMIDIN-7-YL)PHENYL)-N-ETHYL-
Common Name English
ZALEPLON CIV [USP-RS]
Common Name English
LJC 10846
Code English
ZALEPLON [USAN]
Common Name English
L-846
Code English
3'-(3-CYANOPYRAZOLO(1,5-.ALPHA.)PYRIMIDIN-7-YL)-N-ETHYLACETANILIDE
Common Name English
ZALEPLON [MI]
Common Name English
CL 284,846
Code English
LJC-10846
Code English
ZERENE
Brand Name English
SKP-1041
Code English
CL-284846
Code English
ZALEPLON [WHO-DD]
Common Name English
ZALEPLON [VANDF]
Common Name English
ZALEPLON [INN]
Common Name English
ZALEPLON [ORANGE BOOK]
Common Name English
SONATA
Brand Name English
L846
Code English
ZALEPLON [JAN]
Common Name English
ZALEPLON [EMA EPAR]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS SONATA (AUTHORIZED: SLEEP INITIATION AND MAINTENANCE DISORDERS)
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
EMA ASSESSMENT REPORTS ZERENE (WITHDRAWN: SLEEP INITIATION AND MAINTENANCE DISORDERS)
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
NDF-RT N0000183360
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
NCI_THESAURUS C29756
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
DEA NO. 2781
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
WHO-VATC QN05CF03
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
LIVERTOX 1045
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
WHO-ATC N05CF03
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C29551
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
LACTMED
Zaleplon
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
FDA UNII
S62U433RMH
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
USP_CATALOG
1724350
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY USP-RS
CAS
151319-34-5
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
WIKIPEDIA
ZALEPLON
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
RXCUI
74667
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY RxNorm
MESH
C085665
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
ChEMBL
CHEMBL1521
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
IUPHAR
4345
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
DRUG BANK
DB00962
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
DRUG CENTRAL
2857
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
EVMPD
SUB00132MIG
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
EPA CompTox
151319-34-5
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
PUBCHEM
5719
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY
MERCK INDEX
M11579
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY Merck Index
INN
7312
Created by admin on Sat Jun 26 11:34:54 UTC 2021 , Edited by admin on Sat Jun 26 11:34:54 UTC 2021
PRIMARY