Details
Stereochemistry | ACHIRAL |
Molecular Formula | C16H11ClN4 |
Molecular Weight | 294.738 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
ClC1=CC2=C(C=C1)N3C=NN=C3CN=C2C4=CC=CC=C4
InChI
InChIKey=CDCHDCWJMGXXRH-UHFFFAOYSA-N
InChI=1S/C16H11ClN4/c17-12-6-7-14-13(8-12)16(11-4-2-1-3-5-11)18-9-15-20-19-10-21(14)15/h1-8,10H,9H2
DescriptionSources: http://www.drugbank.ca/drugs/DB01215Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/estazolam.html
Sources: http://www.drugbank.ca/drugs/DB01215
Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/estazolam.html
Estazolam, a triazolobenzodiazepine derivative, is an oral hypnotic agent with anticonvulsant, hypnotic, and muscle relaxant properties. It has been shown in some cases to be more potent than diazepam or nitrazepam. Benzodiazepines bind nonspecifically to benzodiazepine receptors, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects GABA by increasing GABA affinity for the GABA receptor. Binding of the inhibitory neurotransmitter GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell. Used for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Marketed under the brand names ProSom, Eurodin.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2093872 Sources: http://www.drugbank.ca/drugs/DB01215 |
|||
Target ID: GO:0070527 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2890779 |
3.8 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Estazolam Approved UseEstazolam is indicated for the short-term management of insomnia characterized by difficulty in falling asleep, frequent nocturnal awakenings, and/or early morning awakenings. Launch Date1997 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
54.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
98.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
194 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
180 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1050 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
2060 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
4343 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
5517 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
14.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1968715/ |
2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
19 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
17 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2862746/ |
2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ESTAZOLAM plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
6 mg 1 times / day single, oral Highest studied dose Dose: 6 mg, 1 times / day Route: oral Route: single Dose: 6 mg, 1 times / day Sources: |
healthy, 21-47 n = 60 Health Status: healthy Age Group: 21-47 Sex: M+F Population Size: 60 Sources: |
|
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: |
unhealthy, 42.9 (18-85) n = 685 Health Status: unhealthy Condition: insomnia Age Group: 42.9 (18-85) Sex: M+F Population Size: 685 Sources: |
Disc. AE: Illness, Somnolence... AEs leading to discontinuation/dose reduction: Illness Sources: Somnolence (grade 1-2) Dizziness (grade 1-2) |
40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Disc. AE: Somnolence, Respiratory depression... AEs leading to discontinuation/dose reduction: Somnolence Sources: Respiratory depression Confusion Coordination impaired Slurred speech Coma |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Illness | Disc. AE | 2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: |
unhealthy, 42.9 (18-85) n = 685 Health Status: unhealthy Condition: insomnia Age Group: 42.9 (18-85) Sex: M+F Population Size: 685 Sources: |
Dizziness | grade 1-2 Disc. AE |
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: |
unhealthy, 42.9 (18-85) n = 685 Health Status: unhealthy Condition: insomnia Age Group: 42.9 (18-85) Sex: M+F Population Size: 685 Sources: |
Somnolence | grade 1-2 Disc. AE |
2 mg 1 times / day multiple, oral Recommended Dose: 2 mg, 1 times / day Route: oral Route: multiple Dose: 2 mg, 1 times / day Sources: |
unhealthy, 42.9 (18-85) n = 685 Health Status: unhealthy Condition: insomnia Age Group: 42.9 (18-85) Sex: M+F Population Size: 685 Sources: |
Coma | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Confusion | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Coordination impaired | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Respiratory depression | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Slurred speech | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Somnolence | Disc. AE | 40 mg 1 times / day single, oral Overdose Dose: 40 mg, 1 times / day Route: oral Route: single Dose: 40 mg, 1 times / day Sources: |
unknown, unknown Health Status: unknown Age Group: unknown Sex: unknown Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
no | |||
yes [Inhibition 10 uM] | ||||
yes [Inhibition 10 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25183402/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
[Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants]. | 1986 Jul |
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Comparative efficacy of estazolam, flurazepam, and placebo in outpatients with insomnia. | 1986 Jul |
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Diazepam-induced decrease in histamine turnover in mouse brain. | 1986 May 27 |
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Inhibition of the binding and the behavioral effects of thyrotropin-releasing hormone (TRH) by the triazolobenzodiazepines. | 1988 May |
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Estazolam treatment of insomnia in generalized anxiety disorder: a placebo-controlled study. | 1991 Aug |
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Metabolic alkalosis and myoclonus from antacid ingestion. | 1996 Jun |
|
Simultaneous analyses of hypoglycemic agents and C-peptide are essential in a homicide case with the combined dosing insulin and insulin-releasing drug. | 2002 Mar |
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Pharmacokinetics and drug interactions of the sedative hypnotics. | 2003 Winter |
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Overview of the therapeutic management of insomnia with zolpidem. | 2004 |
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Simultaneous determination of albendazole and its major active metabolite in human plasma using a sensitive and specific liquid chromatographic-tandem mass spectrometric method. | 2004 Jun 29 |
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Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds. | 2005 |
|
Date-rape drugs scene in Poland. | 2005 |
|
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. | 2005 Dec |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
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Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists. | 2005 Jun 15 |
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TCM treatment for 63 cases of senile dyssomnia. | 2005 Mar |
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Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam. | 2005 May |
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[Effects of midazolam and estazolam as hypnotics in hypertensive patients with chronic insomnia: a multicentre, open labeled, randomized clinical trial]. | 2006 Apr |
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Simultaneous determination of spironolactone and its active metabolite canrenone in human plasma by HPLC-APCI-MS. | 2006 Apr |
|
Determination of four benzodiazepine residues in pork using multiwalled carbon nanotube solid-phase extraction and gas chromatography-mass spectrometry. | 2006 Dec 8 |
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High-performance liquid chromatography-atmospheric pressure chemical ionisation-mass spectrometry determination of zaleplon in human plasma. | 2006 Feb 24 |
|
Sleep maintenance insomnia: strengths and weaknesses of current pharmacologic therapies. | 2006 Jan-Mar |
|
[Analysis of 37 drugs in whole blood by HPLC after solid phase extraction]. | 2006 Oct 15 |
|
Indiplon in the treatment of sleep disorders. | 2007 Dec |
|
[Randomized and controlled study on effect of acupuncture on sleep quality in the patient of primary insomnia]. | 2007 Dec |
|
[Comparative study on treatment of somnipathy in patients with hypertension by traditional Chinese medicine and by estazolam]. | 2007 Feb |
|
High performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI) method for simultaneous determination of venlafaxine and its three metabolites in human plasma. | 2007 May 1 |
|
Sensitive and selective liquid chromatography-tandem mass spectrometry method for the quantification of aniracetam in human plasma. | 2007 Oct 15 |
|
Comparative bioavailability of two estazolam tablet formulations in Indonesian healthy volunteers. | 2008 |
|
Abdominal acupuncture for insomnia in women: a randomized controlled clinical trial. | 2008 |
|
High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics. | 2008 Aug 5 |
|
Long-term stability of various drugs and metabolites in urine, and preventive measures against their decomposition with special attention to filtration sterilization. | 2008 Jan 30 |
|
Simultaneous determination of naringenin and hesperetin in rats after oral administration of Da-Cheng-Qi decoction by high-performance liquid chromatography-tandem mass spectrometry. | 2008 Jul |
|
Auricular acupuncture for insomnia: a systematic review. | 2008 Nov |
|
Simultaneous determination of benzodiazepines and their metabolites in human serum by liquid chromatography-tandem mass spectrometry using a high-resolution octadecyl silica column compatible with aqueous compounds. | 2009 Apr |
|
[Simultaneous determination of 5 sedative hypnotics in human plasma by reversed phase high-performance liquid chromatography]. | 2009 Jul |
|
Forty cases of insomnia treated by suspended moxibustion at Baihui (GV 20). | 2009 Jun |
|
[Effect of modified xiaoyao powder for improving sleep in patients with psychological stress insomnia]. | 2009 Mar |
|
[Analysis on somnipathy related factors in elderly patients with stroke and comparative study on the efficacy of treatment by traditional Chinese medicine and by estazolam]. | 2009 Mar |
|
Algorithms for the assessment and management of insomnia in primary care. | 2009 Nov 3 |
|
Drugs associated with more suicidal ideations are also associated with more suicide attempts. | 2009 Oct 2 |
|
The XIA's No. 1 sleeping Prescription for the treatment of insomnia of the deficiency type: a clinical observation of 60 cases. | 2009 Sep |
|
Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. | 2009 Winter |
|
Four cases of dysthymic disorder and general malaise successfully treated with traditional herbal (kampo) medicines: kamiuntanto. | 2010 |
|
5-(4-Chloro-phen-yl)-3-(2,4-dimethyl-thiazol-5-yl)-1,2,4-triazolo[3,4-a]isoquinoline. | 2010 Apr 10 |
|
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010 Dec |
|
[The influence of estazolam on human neurobehavioral function]. | 2010 Feb |
|
[Clinical observation on acupoint catgut embedding at head-acupoint combined with massage of sole for treatment of refractory insomnia]. | 2010 Feb |
|
Management of tinea capitis in childhood. | 2010 Jul 14 |
|
A validated method for simultaneous screening and quantification of twenty-three benzodiazepines and metabolites plus zopiclone and zaleplone in whole blood by liquid-liquid extraction and ultra-performance liquid chromatography- tandem mass spectrometry. | 2010 Jul-Aug |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/pro/estazolam.html
Usual Adult Dose for Insomnia
1 to 2 mg orally at bedtime
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2890779
Incubation of rabbit PRP with etizolam for 2 min before administration of aggregating agents inhibited aggregation induced by PAF (190 nM) with
an IC50 of 3.8 uM. Etizolam at a higher concentration (300 uM) only slightly in
hibited ADP (15 uM) and arachidonic acid-induced aggregation
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1012
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WHO-ATC |
N05CD04
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NDF-RT |
N0000007542
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LIVERTOX |
NBK548660
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WHO-VATC |
QN05CD04
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NDF-RT |
N0000175694
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DEA NO. |
2756
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C47520
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D004949
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CC-24
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3261
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36S3EQV54C
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SUB07241MIG
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1056
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1249905
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7550
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4077
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PRIMARY | RxNorm | ||
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Estazolam
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DB01215
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100000082361
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ESTAZOLAM
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CHEMBL285674
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36S3EQV54C
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3611
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249-982-4
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m5027
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DTXSID5020572
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290818
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4858
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29975-16-4
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE LESS ACTIVE (PARENT)