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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
Structure of MIDAZOLAM MALEATE

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-

HIDE SMILES / InChI
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.

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

1985
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

1985
Primary
Midafresa

Approved Use

Epilepsy

Launch Date

2014
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
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...
Other AEs:
Nausea
Hypotension
Sources:
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)
Somnolence (1 patient)
Other AEs:
Nasal discomfort (12.4%)
Somnolence (9.3%)
Sources:
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)
Hypotension (5 patients)
Sources:
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%)
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
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

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
Binding, partial agonism, and potentiation of alpha(1)-adrenergic receptor function by benzodiazepines: A potential site of allosteric modulation.
1999 Dec
Anticonvulsants for soman-induced seizure activity.
1999 Mar-Apr
Flumazenil antagonizes midazolam-induced airway narrowing during nasal breathing in humans.
1999 May
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
Computerised advice on drug dosage to improve prescribing practice.
2001
Propofol vs midazolam for ICU sedation : a Canadian multicenter randomized trial.
2001 Apr
Using intranasal midazolam spray to prevent claustrophobia induced by MR imaging.
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
Triazolam discrimination in squirrel monkeys distinguishes high-efficacy agonists from other benzodiazepines and non-benzodiazepine drugs.
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
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
[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
[Anesthetic experience of emergency coronary artery bypass graft operation in a patient with cardioamyloidosis].
2001 Jan
[Anesthetic management for mitral valve replacement in a patient with idiopathic hypereosinophilic syndrome].
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
Etomidate for pediatric sedation prior to fracture reduction.
2001 Jan
Adrenocortical dysfunction following etomidate induction in emergency department patients.
2001 Jan
Speed of recovery and side-effect profile of sevoflurane sedation compared with midazolam.
2001 Jan
Awake craniotomy for removal of intracranial tumor: considerations for early discharge.
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 should be preferred to nasal midazolam.
2001 Jan 13
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
The comparison of midazolam and topical lidocaine spray versus the combination of midazolam, meperidine, and topical lidocaine spray to sedate patients for upper endoscopy.
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
Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation.
2001 Mar-Apr
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
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.
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
RO 21-3981/001
Code English
RO-213981-003
Code English
Midazolam maleate [WHO-DD]
Common Name 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 Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY RxNorm
DRUG BANK
DBSALT002303
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
CAS
59467-94-6
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
ChEMBL
CHEMBL655
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
SMS_ID
100000076068
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
NSC
313452
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
EVMPD
SUB14573MIG
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
NCI_THESAURUS
C167002
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
ECHA (EC/EINECS)
261-775-0
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
MERCK INDEX
m7531
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY Merck Index
FDA UNII
77520S18SE
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY
PUBCHEM
5384200
Created by admin on Fri Dec 15 15:23:37 GMT 2023 , Edited by admin on Fri Dec 15 15:23:37 GMT 2023
PRIMARY