Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H13ClFN3.C4H4O4 |
Molecular Weight | 441.839 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)\C=C/C(O)=O.CC1=NC=C2CN=C(C3=C(F)C=CC=C3)C4=C(C=CC(Cl)=C4)N12
InChI
InChIKey=XYGVIBXOJOOCFR-BTJKTKAUSA-N
InChI=1S/C18H13ClFN3.C4H4O4/c1-11-21-9-13-10-22-18(14-4-2-3-5-16(14)20)15-8-12(19)6-7-17(15)23(11)13;5-3(6)1-2-4(7)8/h2-9H,10H2,1H3;1-2H,(H,5,6)(H,7,8)/b;2-1-
Midazolam, previously marketed under the trade name Versed, is a medication used for anesthesia, procedural sedation, trouble sleeping, and severe agitation. Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Pharmacodynamic properties of midazolam and its metabolites, which are similar to those of other benzodiazepines, include sedative, anxiolytic, amnesic and hypnotic activities. Benzodiazepine pharmacologic effects appear to result from reversible interactions with the γ-amino butyric acid (GABA) benzodiazepine receptor in the CNS, the major inhibitory neurotransmitter in the central nervous system. The action of midazolam is readily reversed by the benzodiazepine receptor antagonist, flumazenil.
Data from published reports of studies in pediatric patients clearly demonstrate that oral midazolam provides safe and effective sedation and anxiolysis prior to surgical procedures that require anesthesia as well as before other procedures that require sedation but may not require anesthesia. The most commonly reported effective doses range from 0.25 to 1 mg/kg in children (6 months to <16 years). The single most commonly reported effective dose is 0.5 mg/kg. Time to onset of effect is most frequently reported as 10 to 20 minutes.
The effects of midazolam on the CNS are dependent on the dose administered, the route of administration, and the presence or absence of other medications.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
2.0 nM [Ki] | |||
Target ID: CHEMBL1810 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2566295 |
3.2 µM [Ki] | ||
Target ID: CHEMBL232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10565838 |
183.0 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Midazolam Approved UseMidazolam hydrochloride syrup is indicated for use in pediatric patients for sedation, anxiolysis and amnesia prior to diagnostic, therapeutic or endoscopic procedures or before induction of anesthesia.
Midazolam hydrochloride syrup is intended for use in monitored settings only and not for chronic or home use (see WARNINGS). MIDAZOLAM HYDROCHLORIDE SYRUP MUST BE USED AS SPECIFIED IN THE LABEL.
Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours Launch Date1985 |
|||
Primary | Midazolam Approved UseMidazolam HCl syrup is indicated for use in pediatric patients for sedation, anxiolysis and amnesia prior to diagnostic, therapeutic or endoscopic procedures or before induction of anesthesia. Midazolam HCl syrup is intended for use in monitored settings only and not for chronic or home use (see WARNINGS). MIDAZOLAM HCl SYRUP MUST BE USED AS SPECIFIED IN THE LABEL. Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours Launch Date1985 |
|||
Primary | Midafresa Approved UseEpilepsy Launch Date2014 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
54.7 ng/mL |
5 mg single, nasal dose: 5 mg route of administration: Nasal experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
113.9 ng/mL |
10 mg single, intramuscular dose: 10 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
35.124 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01989169 |
6 mg single, oral dose: 6 mg route of administration: oral experiment type: single co-administered: |
MIDAZOLAM plasma | Homo sapiens population: healthy age: Adults sex: food status: |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
126.2 ng × h/mL |
5 mg single, nasal dose: 5 mg route of administration: Nasal experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
402.7 ng × h/mL |
10 mg single, intramuscular dose: 10 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
100.935 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01989169 |
6 mg single, oral dose: 6 mg route of administration: oral experiment type: single co-administered: |
MIDAZOLAM plasma | Homo sapiens population: healthy age: Adults sex: food status: |
|
103.348 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01989169 |
6 mg single, oral dose: 6 mg route of administration: oral experiment type: single co-administered: |
MIDAZOLAM plasma | Homo sapiens population: healthy age: Adults sex: food status: |
|
30 nM*h Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01361217 |
2 mg single, oral dose: 2 mg route of administration: oral experiment type: single co-administered: |
MIDAZOLAM plasma | Homo sapiens population: healthy age: adults sex: food status: |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3% |
5 mg single, nasal dose: 5 mg route of administration: Nasal experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
3% |
10 mg single, intramuscular dose: 10 mg route of administration: Intramuscular experiment type: SINGLE co-administered: |
MIDAZOLAM unknown | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
5 mg single, intranasal MTD Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Co-administed with:: sufentanil(0.4 mg/kg) Sources: |
unknown, 18 - 65 years n = 30 Health Status: unknown Condition: gastroscopy Age Group: 18 - 65 years Sex: unknown Population Size: 30 Sources: |
Other AEs: Nausea, Hypotension... |
5 mg 1 times / month multiple, intranasal (mean) Recommended Dose: 5 mg, 1 times / month Route: intranasal Route: multiple Dose: 5 mg, 1 times / month Sources: |
unhealthy, > 12 years n = 161 Health Status: unhealthy Condition: seizure clusters Age Group: > 12 years Sex: unknown Population Size: 161 Sources: |
Disc. AE: Nasal discomfort, Somnolence... Other AEs: Nasal discomfort, Somnolence... AEs leading to discontinuation/dose reduction: Nasal discomfort (1 patient) Other AEs:Somnolence (1 patient) Nasal discomfort (12.4%) Sources: Somnolence (9.3%) |
5 mg single, intranasal (mean) Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unknown, adult and children n = 87740 Health Status: unknown Condition: gastroscopy Age Group: adult and children Sex: M+F Population Size: 87740 Sources: |
Other AEs: Hypoxemia, Hypotension... Other AEs: Hypoxemia (90 patients) Sources: Hypotension (5 patients) |
5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Other AEs: Somnolence, Headache... Other AEs: Somnolence (10%) Sources: Headache (7%) Dysarthria (2%) Nasal discomfort (5%) Throat irritation (2%) Rhinorrhea (3%) Lacrimation increased (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | 5 mg single, intranasal MTD Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Co-administed with:: sufentanil(0.4 mg/kg) Sources: |
unknown, 18 - 65 years n = 30 Health Status: unknown Condition: gastroscopy Age Group: 18 - 65 years Sex: unknown Population Size: 30 Sources: |
|
Nausea | 5 mg single, intranasal MTD Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Co-administed with:: sufentanil(0.4 mg/kg) Sources: |
unknown, 18 - 65 years n = 30 Health Status: unknown Condition: gastroscopy Age Group: 18 - 65 years Sex: unknown Population Size: 30 Sources: |
|
Nasal discomfort | 1 patient Disc. AE |
5 mg 1 times / month multiple, intranasal (mean) Recommended Dose: 5 mg, 1 times / month Route: intranasal Route: multiple Dose: 5 mg, 1 times / month Sources: |
unhealthy, > 12 years n = 161 Health Status: unhealthy Condition: seizure clusters Age Group: > 12 years Sex: unknown Population Size: 161 Sources: |
Somnolence | 1 patient Disc. AE |
5 mg 1 times / month multiple, intranasal (mean) Recommended Dose: 5 mg, 1 times / month Route: intranasal Route: multiple Dose: 5 mg, 1 times / month Sources: |
unhealthy, > 12 years n = 161 Health Status: unhealthy Condition: seizure clusters Age Group: > 12 years Sex: unknown Population Size: 161 Sources: |
Nasal discomfort | 12.4% | 5 mg 1 times / month multiple, intranasal (mean) Recommended Dose: 5 mg, 1 times / month Route: intranasal Route: multiple Dose: 5 mg, 1 times / month Sources: |
unhealthy, > 12 years n = 161 Health Status: unhealthy Condition: seizure clusters Age Group: > 12 years Sex: unknown Population Size: 161 Sources: |
Somnolence | 9.3% | 5 mg 1 times / month multiple, intranasal (mean) Recommended Dose: 5 mg, 1 times / month Route: intranasal Route: multiple Dose: 5 mg, 1 times / month Sources: |
unhealthy, > 12 years n = 161 Health Status: unhealthy Condition: seizure clusters Age Group: > 12 years Sex: unknown Population Size: 161 Sources: |
Hypotension | 5 patients | 5 mg single, intranasal (mean) Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unknown, adult and children n = 87740 Health Status: unknown Condition: gastroscopy Age Group: adult and children Sex: M+F Population Size: 87740 Sources: |
Hypoxemia | 90 patients | 5 mg single, intranasal (mean) Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unknown, adult and children n = 87740 Health Status: unknown Condition: gastroscopy Age Group: adult and children Sex: M+F Population Size: 87740 Sources: |
Lacrimation increased | 1% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Somnolence | 10% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Dysarthria | 2% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Throat irritation | 2% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Rhinorrhea | 3% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Nasal discomfort | 5% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Headache | 7% | 5 mg single, intranasal Recommended Dose: 5 mg Route: intranasal Route: single Dose: 5 mg Sources: |
unhealthy, adult n = 91 Health Status: unhealthy Condition: intermittent, stereotypic episodes of frequent seizure activity Age Group: adult Sex: unknown Population Size: 91 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [Ki 3.7 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/15544435/ Page: 9.0 |
yes [Ki 5.8 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211321Orig1s000ClinPharmR.pdf#page=11 Page: 11,12 |
major | yes (co-administration study) Comment: INHIBITORS: Coadministration with cimetidine: AUC increase of MDZ=10-102%; diltiazem: AUC increase of MDZ=275%; erythromycin: AUC increase of MDZ=281-341; fluconazole: AUC increase of MDZ=250%; grapefruit juice: AUC increase of 52%; itraconazole: AUC increase of MDZ=240-980%; ketoconazole: AUC increase of MDZ=1490%; ranitidine: AUC increase of MDZ=9-66%. INDUCERS: coadministration with carbamazepine: AUC decrease of MDZ=94%; phenytoin: AUC decrease of MDZ=94%; rifampin: AUC decrease of MDZ=96%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211321Orig1s000ClinPharmR.pdf#page=11 Page: 11,12 |
||
minor | ||||
minor | ||||
minor | ||||
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
no | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/18256203/ Page: 8.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Computerised advice on drug dosage to improve prescribing practice. | 2001 |
|
A lack of evidence of superiority of propofol versus midazolam for sedation in mechanically ventilated critically ill patients: a qualitative and quantitative systematic review. | 2001 Apr |
|
The preemptive analgesic effect of intraarticular bupivacaine and morphine after ambulatory arthroscopic knee surgery. | 2001 Apr |
|
Stress response in infants undergoing cardiac surgery: a randomized study of fentanyl bolus, fentanyl infusion, and fentanyl-midazolam infusion. | 2001 Apr |
|
Using intranasal midazolam spray to prevent claustrophobia induced by MR imaging. | 2001 Apr |
|
Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons. | 2001 Apr |
|
Metabolism of levo-alpha-Acetylmethadol (LAAM) by human liver cytochrome P450: involvement of CYP3A4 characterized by atypical kinetics with two binding sites. | 2001 Apr |
|
Prediction of midazolam-CYP3A inhibitors interaction in the human liver from in vivo/in vitro absorption, distribution, and metabolism data. | 2001 Apr |
|
Sedation for cataract surgery. | 2001 Feb |
|
Preparation, premedication, and surveillance. | 2001 Feb |
|
[Epileptogenic drugs in anesthesia]. | 2001 Feb |
|
Propofol as a continuous infusion during cardiopulmonary bypass does not affect changes in serum free fatty acids. | 2001 Feb |
|
Small doses of remifentanil or sufentanil for blunting cardiovascular changes induced by tracheal intubation: a double-blind comparison. | 2001 Feb |
|
Bilateral frontal haemorrhages associated with continuous spinal analgesia. | 2001 Feb |
|
The use of thiopentone/propofol admixture for laryngeal mask airway insertion. | 2001 Feb |
|
Transdermal delivery of antisense oligonucleotides can induce changes in gene expression in vivo. | 2001 Feb |
|
[Fastrach laryngeal mask, sevoflurane and remifentanil: an anesthetic alternative for the myasthenic patient]. | 2001 Feb |
|
Pharmacoeconomic assessment of propofol 2% used for prolonged sedation. | 2001 Feb |
|
[Anesthetic management for the correction of pectus excavatum using pectus bar under video-assistance]. | 2001 Feb |
|
[Anesthetic management for left ventricular assist device implantation in patients waiting for heart transplantation]. | 2001 Feb |
|
A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection. | 2001 Feb |
|
Oral transmucosal midazolam premedication for preschool children. | 2001 Feb |
|
Cardiovascular effects of sevoflurane, isoflurane, halothane, and fentanyl-midazolam in children with congenital heart disease: an echocardiographic study of myocardial contractility and hemodynamics. | 2001 Feb |
|
Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults. | 2001 Feb |
|
Monitoring of end-tidal carbon dioxide partial pressure changes during infrarenal aortic cross-clamping: a non-invasive method to predict unclamping hypotension. | 2001 Feb |
|
In situ nasal absorption of midazolam in rats. | 2001 Feb 1 |
|
[Premedication for endoscopy]. | 2001 Feb 2 |
|
Sedation for children requiring wound repair: a randomised controlled double blind comparison of oral midazolam and oral ketamine. | 2001 Jan |
|
Intra-nasal midazolam in conscious sedation of young paediatric dental patients. | 2001 Jan |
|
Ketamine-midazolam total intravenous anaesthesia for prolonged abdominal surgery. | 2001 Jan |
|
Pulse oximetry saturation levels during routine unsedated diagnostic upper gastrointestinal endoscopy. | 2001 Jan |
|
[Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome]. | 2001 Jan |
|
Propofol versus midazolam regarding their antioxidant activities. | 2001 Jan |
|
Influence of patient posture on oxygen saturation during fibre-optic bronchoscopy. | 2001 Jan |
|
The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients. | 2001 Jan |
|
Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray. | 2001 Jan 5 |
|
A retrospective study on the effectiveness of intranasal midazolam in pediatric burn patients. | 2001 Jan-Feb |
|
Patient status and time to intubation in the assessment of prehospital intubation performance. | 2001 Jan-Mar |
|
Synergistic analgesic effects of intrathecal midazolam and NMDA or AMPA receptor antagonists in rats. | 2001 Mar |
|
Selective spinal anesthesia for outpatient laparoscopy. II: epinephrine and spinal cord function. | 2001 Mar |
|
Drugs and syringe drivers: a survey of adult specialist palliative care practice in the United Kingdom and Eire. | 2001 Mar |
|
Midazolam reduces the dose of propofol required for induction of anaesthesia and laryngeal mask airway insertion. | 2001 Mar |
|
Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity. | 2001 Mar |
|
Comparison of midazolam with or without fentanyl for conscious sedation and hemodynamics in coronary angiography. | 2001 Mar |
|
Anaesthetic technique for transoesophageal echocardiography in children. | 2001 Mar |
|
Propofol is not effective for hyperventilation syndrome. | 2001 Mar |
|
The effect of anxiety and personality on the pharmacokinetics of oral midazolam. | 2001 Mar |
|
Evaluation of the safety and efficacy of repeated sedations for the radiotherapy of young children with cancer: a prospective study of 1033 consecutive sedations. | 2001 Mar 1 |
|
Onset and duration of action of rocuronium--from tracheal intubation, through intense block to complete recovery. | 2001 May |
|
Inhibition of CYP3A4 in a rapid microtiter plate assay using recombinant enzyme and in human liver microsomes using conventional substrates. | 2001 May |
Patents
Sample Use Guides
Midazolam hydrochloride syrup is indicated for use as a single dose (0.25 to 1 mg/kg with a maximum dose of 20 mg) for preprocedural sedation and anxiolysis in pediatric patients. Midazolam hydrochloride syrup is not intended for chronic administration.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8173965
Midazolam (1 uM) decreased GABA-activated currents in acutely dissociated neurons, isolated from the medial septum/nucleus of the diagonal band (MS/nDB) of the adult rat brains.
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142441
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DBSALT002303
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59467-94-6
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CHEMBL655
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100000076068
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313452
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SUB14573MIG
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C167002
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261-775-0
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m7531
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77520S18SE
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5384200
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD