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-
Molecular Formula | C4H4O4 |
Molecular Weight | 116.0722 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
Molecular Formula | C18H13ClFN3 |
Molecular Weight | 325.767 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 |
---|---|---|
Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation. | 1999 Dec |
|
A double-blind placebo controlled trial of oral midazolam as premedication before flexible sigmoidoscopy. | 1999 Nov |
|
No reduction in the sufentanil requirement of elderly patients undergoing ventilatory support in the medical intensive care unit. | 1999 Oct |
|
Myoclonic movements in very low birth weight premature infants associated with midazolam intravenous bolus administration. | 1999 Sep |
|
Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells. | 2000 Jun |
|
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 |
|
Using intranasal midazolam spray to prevent claustrophobia induced by MR imaging. | 2001 Apr |
|
Prediction of midazolam-CYP3A inhibitors interaction in the human liver from in vivo/in vitro absorption, distribution, and metabolism data. | 2001 Apr |
|
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs. | 2001 Feb |
|
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 |
|
Pharmacoeconomic assessment of propofol 2% used for prolonged sedation. | 2001 Feb |
|
[Anesthetic management for left ventricular assist device implantation in patients waiting for heart transplantation]. | 2001 Feb |
|
Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transport. | 2001 Feb |
|
Effect of midazolam pretreatment on induction dose requirements of propofol in combination with fentanyl in younger and older adults. | 2001 Feb |
|
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone. | 2001 Feb |
|
Propofol depressed neutrophil hydrogen peroxide production more than midazolam, whereas adhesion molecule expression was minimally affected by both anesthetics in rats with abdominal sepsis. | 2001 Feb |
|
In situ nasal absorption of midazolam in rats. | 2001 Feb 1 |
|
[Premedication in ambulatory surgery]. | 2001 Feb 12 |
|
[Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome]. | 2001 Jan |
|
[The influence of age on hemodynamics and the dose requirements of propofol and buprenorphine in total intravenous anesthesia]. | 2001 Jan |
|
Propofol versus midazolam regarding their antioxidant activities. | 2001 Jan |
|
Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers. | 2001 Jan |
|
A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. | 2001 Jan |
|
Minimum local anesthetic volume blocking the femoral nerve in 50% of cases: a double-blinded comparison between 0.5% ropivacaine and 0.5% bupivacaine. | 2001 Jan |
|
Awake craniotomy for removal of intracranial tumor: considerations for early discharge. | 2001 Jan |
|
S(+)-ketamine for rectal premedication in children. | 2001 Jan |
|
A comparison of oral clonidine and oral midazolam as preanesthetic medications in the pediatric tonsillectomy patient. | 2001 Jan |
|
A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. | 2001 Jan |
|
Intranasal midazolam for treating febrile seizures in children. Buccal midazolam for childhood seizures at home preferred to rectal diazepam. | 2001 Jan 13 |
|
Intranasal midazolam for treating febrile seizures in children. Buccal midazolam should be preferred to nasal midazolam. | 2001 Jan 13 |
|
Intranasal midazolam for treating febrile seizures in children. Caution is advised in interpreting trial conclusions. | 2001 Jan 13 |
|
The anxiolytic effects of intra-hippocampal midazolam are antagonized by intra-septal L-glutamate. | 2001 Jan 5 |
|
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 |
|
Re: Koshy et al.--The use of propofol versus midazolam. | 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 |
|
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 |
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.
Substance Class |
Chemical
Created
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admin
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Edited
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Record UNII |
77520S18SE
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Record Status |
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Record Version |
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DBSALT002303
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ACTIVE MOIETY |