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

Details

Stereochemistry ACHIRAL
Molecular Formula C18H13ClFN3.C4H4O4
Molecular Weight 441.8403
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of MIDAZOLAM MALEATE

SMILES

Cc1ncc2CN=C(c3ccccc3F)c4cc(ccc4-n12)Cl.C(\[H])(=C(\[H])/C(=O)O)/C(=O)O

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-

HIDE SMILES / InChI

Molecular Formula C18H13ClFN3
Molecular Weight 325.7679
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C4H4O4
Molecular Weight 116.0723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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.

CNS Activity

Curator's Comment:: Midazolam is a benzodiazepine. It works in the central nervous system (brain) to cause sleepiness, muscle relaxation, and short-term memory loss, and to reduce anxiety.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Midazolam

Approved Use

Midazolam 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 Date

503884800000
Primary
Midazolam

Approved Use

Midazolam 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 Date

503884800000
Primary
Midafresa

Approved Use

Epilepsy

Launch Date

1418774400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
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
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse events​
5 mg single, intranasal
MTD
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, 18 - 65 years
Health Status: unknown
Age Group: 18 - 65 years
Sex: unknown
Sources:
Other AEs: Nausea, Hypotension...
Other AEs:
Nausea
Hypotension
Sources:
5 mg 1 times / month multiple, intranasal
Recommended
Dose: 5 mg, 1 times / month
Route: intranasal
Route: multiple
Dose: 5 mg, 1 times / month
Sources:
unhealthy, > 12 years
Health Status: unhealthy
Age Group: > 12 years
Sex: unknown
Sources:
Disc. AE: Nasal discomfort, Somnolence...
Other AEs: Nasal discomfort, Somnolence...
AEs leading to
discontinuation/dose reduction:
Nasal discomfort (1 patient)
Somnolence (1 patient)
Other AEs:
Nasal discomfort (12.4%)
Somnolence (9.3%)
Sources:
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, adult and children
Health Status: unknown
Age Group: adult and children
Sex: M+F
Sources:
Other AEs: Hypoxemia, Hypotension...
Other AEs:
Hypoxemia (90 patients)
Hypotension (5 patients)
Sources:
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Somnolence, Headache...
Other AEs:
Somnolence (10%)
Headache (7%)
Dysarthria (2%)
Nasal discomfort (5%)
Throat irritation (2%)
Rhinorrhea (3%)
Lacrimation increased (1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypotension
5 mg single, intranasal
MTD
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, 18 - 65 years
Health Status: unknown
Age Group: 18 - 65 years
Sex: unknown
Sources:
Nausea
5 mg single, intranasal
MTD
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, 18 - 65 years
Health Status: unknown
Age Group: 18 - 65 years
Sex: unknown
Sources:
Nasal discomfort 1 patient
Disc. AE
5 mg 1 times / month multiple, intranasal
Recommended
Dose: 5 mg, 1 times / month
Route: intranasal
Route: multiple
Dose: 5 mg, 1 times / month
Sources:
unhealthy, > 12 years
Health Status: unhealthy
Age Group: > 12 years
Sex: unknown
Sources:
Somnolence 1 patient
Disc. AE
5 mg 1 times / month multiple, intranasal
Recommended
Dose: 5 mg, 1 times / month
Route: intranasal
Route: multiple
Dose: 5 mg, 1 times / month
Sources:
unhealthy, > 12 years
Health Status: unhealthy
Age Group: > 12 years
Sex: unknown
Sources:
Nasal discomfort 12.4%
5 mg 1 times / month multiple, intranasal
Recommended
Dose: 5 mg, 1 times / month
Route: intranasal
Route: multiple
Dose: 5 mg, 1 times / month
Sources:
unhealthy, > 12 years
Health Status: unhealthy
Age Group: > 12 years
Sex: unknown
Sources:
Somnolence 9.3%
5 mg 1 times / month multiple, intranasal
Recommended
Dose: 5 mg, 1 times / month
Route: intranasal
Route: multiple
Dose: 5 mg, 1 times / month
Sources:
unhealthy, > 12 years
Health Status: unhealthy
Age Group: > 12 years
Sex: unknown
Sources:
Hypotension 5 patients
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, adult and children
Health Status: unknown
Age Group: adult and children
Sex: M+F
Sources:
Hypoxemia 90 patients
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unknown, adult and children
Health Status: unknown
Age Group: adult and children
Sex: M+F
Sources:
Lacrimation increased 1%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Somnolence 10%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dysarthria 2%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Throat irritation 2%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Rhinorrhea 3%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nasal discomfort 5%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Headache 7%
5 mg single, intranasal
Recommended
Dose: 5 mg
Route: intranasal
Route: single
Dose: 5 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Overview

Overview

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Ki 3.7 uM]
yes [Ki 5.8 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
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%;
Page: 11,12
minor
minor
minor
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Midazolam-induced hyperalgesia in rats: modulation via GABA(A) receptors at supraspinal level.
1999 Apr 1
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
Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells.
2000 Jun
Midazolam attenuates ketamine-induced abnormal perception and thought process but not mood changes.
2000 Sep
Computerised advice on drug dosage to improve prescribing practice.
2001
Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial.
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
Prediction of midazolam-CYP3A inhibitors interaction in the human liver from in vivo/in vitro absorption, distribution, and metabolism data.
2001 Apr
[Epileptogenic drugs in anesthesia].
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
[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
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
[Premedication for endoscopy].
2001 Feb 2
Ketamine-midazolam total intravenous anaesthesia for prolonged abdominal surgery.
2001 Jan
[Anesthetic experience of emergency coronary artery bypass graft operation in a patient with cardioamyloidosis].
2001 Jan
[The influence of age on hemodynamics and the dose requirements of propofol and buprenorphine in total intravenous anesthesia].
2001 Jan
Influence of patient posture on oxygen saturation during fibre-optic bronchoscopy.
2001 Jan
Digitally assisted acromioplasty: the effect of interscalene block on this new surgical technique.
2001 Jan
Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers.
2001 Jan
Dexamethasone facilitates discharge after outpatient anorectal surgery.
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
Parental perceptions of comfort during mechanical ventilation.
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
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
Selective spinal anesthesia for outpatient laparoscopy. II: epinephrine and spinal cord function.
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
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
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
by admin
on Fri Jun 25 22:12:37 UTC 2021
Edited
by admin
on Fri Jun 25 22:12:37 UTC 2021
Record UNII
77520S18SE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MIDAZOLAM MALEATE
MART.   MI   USAN   WHO-DD  
USAN  
Official Name English
MIDAZOLAM MALEATE [MART.]
Common Name English
NSC-313452
Code English
4H-IMIDAZO(1,5-A)(1,4)BENZODIAZEPINE, 8-CHLORO-6-(2-FLUOROPHENYL)-1-METHYL-, (Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
MIDAZOLAM (AS MALEATE)
Common Name English
MIDAZOLAM MALEATE [USAN]
Common Name English
MIDAZOLAM MALEATE [WHO-DD]
Common Name English
RO 21-3981/001
Code English
RO-213981-003
Code English
MIDAZOLAM MALEATE [MI]
Common Name English
8-CHLORO-6-(O-FLUOROPHENYL)-1-METHYL-4H-IMIDAZO(1,5-A)(1,4)BENZODIAZEPINE MALEATE (1:1)
Common Name English
RO-21-3981/001
Code English
Code System Code Type Description
RXCUI
142441
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY RxNorm
DRUG BANK
DBSALT002303
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
CAS
59467-94-6
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
ChEMBL
CHEMBL655
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
EVMPD
SUB14573MIG
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
NCI_THESAURUS
C167002
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
ECHA (EC/EINECS)
261-775-0
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
MERCK INDEX
M7531
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY Merck Index
FDA UNII
77520S18SE
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
PUBCHEM
5384200
Created by admin on Fri Jun 25 22:12:37 UTC 2021 , Edited by admin on Fri Jun 25 22:12:37 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY