Details
Stereochemistry | ACHIRAL |
Molecular Formula | C17H15N5O |
Molecular Weight | 305.3339 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN(C(C)=O)C1=CC=CC(=C1)C2=CC=NC3=C(C=NN23)C#N
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
DescriptionCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00962
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2111392 |
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Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12231378 |
169.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Sonata Approved UseSonata is indicated for the short-term treatment of insomnia. Launch Date1999 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
26.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.08 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10211871 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
40% |
ZALEPLON plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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 Other AEs:Suicide Anaphylactic reaction (severe) Anaphylactoid reaction (severe) Angioedema (grade 3-5) Abnormal thinking Sources: Page: p.5Abnormal behavior Amnesia Depression worsened Suicidal tendency |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: - |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/9604298/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9604298/ Page: - |
no | |||
Page: 10.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9604298/ Page: - |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9604298/ Page: - |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20859_Sonata_clinphrmr.pdf#page=6 Page: 6.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20859_Sonata_clinphrmr.pdf#page=6 Page: 6.0 |
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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/99/20859_Sonata_clinphrmr.pdf#page=6 Page: 6.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Zaleplon improves sleep quality in maintenance hemodialysis patients. | 2003 |
|
Clinically important drug interactions with zopiclone, zolpidem and zaleplon. | 2003 |
|
Gaboxadol: in vitro interaction studies with benzodiazepines and ethanol suggest functional selectivity. | 2003 Apr 25 |
|
Impact of melatonin, zaleplon, zopiclone, and temazepam on psychomotor performance. | 2003 Dec |
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Changes in GABA(A) receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal. | 2003 Dec 17 |
|
[Poisonings with benzodiazepine-like drugs]. | 2003 Feb 20 |
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[In cases of coma and blue-green urine should overdosage of zaleplon be considered. First case reports]. | 2003 Feb 20 |
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Preference of insomniac patients between a single dose of zolpidem 10 mg versus zaleplon 10 mg. | 2003 Jul |
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Mixed drug intoxication involving zaleplon ("Sonata"). | 2003 Jul 8 |
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Ziprasidone metabolism, aldehyde oxidase, and clinical implications. | 2003 Jun |
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Determination of zaleplon and zolpidem by liquid chromatography-turbo-ionspray mass spectrometry: application to forensic cases. | 2003 Jun 5 |
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Anxiolysis in general dental practice. | 2003 Mar |
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Zaleplon and driving impairment. | 2003 May |
|
Efficacy, safety and cost of new drugs acting on the central nervous system. | 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 |
|
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 |
|
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 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12231378
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.
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
SONATA (AUTHORIZED: SLEEP INITIATION AND MAINTENANCE DISORDERS)
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EMA ASSESSMENT REPORTS |
ZERENE (WITHDRAWN: SLEEP INITIATION AND MAINTENANCE DISORDERS)
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NDF-RT |
N0000183360
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NCI_THESAURUS |
C29756
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DEA NO. |
2781
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WHO-VATC |
QN05CF03
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LIVERTOX |
NBK548924
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WHO-ATC |
N05CF03
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C29551
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Zaleplon
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S62U433RMH
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100000088001
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151319-34-5
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ZALEPLON
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10102
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74667
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C085665
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CHEMBL1521
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4345
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DB00962
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1724350
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2857
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GG-36
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S62U433RMH
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SUB00132MIG
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DTXSID5023748
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5719
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m11579
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7312
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)
METABOLITE INACTIVE (PARENT)