ContaminantDB: Midazolam

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (23)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:27:24 UTC

Update Date

2026-03-26 18:33:06 UTC

Accession Number

CHEM002247

Identification

Common Name

Midazolam

Class

Small Molecule

Description

A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH. [PubChem] Midazolam is a schedule IV drug in the United States.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
Suspected Compounds
T3DB toxins

Contaminant Type

Adjuvant, Anesthesia
Anesthetic, Intravenous
Anti-Anxiety Agent
Drug
GABA Modulator
Hypnotic and Sedative
Metabolite
Organic Compound
Organochloride
Organofluoride
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Buccolam	ChEBI
Dormicum	ChEBI
Mezolam	ChEBI
Midazolamum	ChEBI
Nayzilam	Kegg
Dea no. 2884	HMDB
Midazolam base	HMDB
Maleate, midazolam	HMDB
Midazolam maleate	HMDB
Hydrochloride, midazolam	HMDB
Midazolam hydrochloride	HMDB
Versed	HMDB

Chemical Formula

C₁₈H₁₃ClFN₃

Average Molecular Mass

325.767 g/mol

Monoisotopic Mass

325.078 g/mol

CAS Registry Number

59467-70-8

IUPAC Name

12-chloro-9-(2-fluorophenyl)-3-methyl-2,4,8-triazatricyclo[8.4.0.0²,⁶]tetradeca-1(10),3,5,8,11,13-hexaene

Traditional Name

midazolam

SMILES

CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12

InChI Identifier

InChI=1S/C18H13ClFN3/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/h2-9H,10H2,1H3

InChI Key

DDLIGBOFAVUZHB-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as imidazo[1,5-a][1,4]benzodiazepines. Imidazo[1,5-a][1,4]benzodiazepines are compounds containing an imidazole ring and a 1,4-benzodiazepine ring system, both sharing one nitrogen atom.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzodiazepines

Sub Class

1,4-benzodiazepines

Direct Parent

Imidazo[1,5-a][1,4]benzodiazepines

Alternative Parents

Substituents

Imidazo[1,5-a][1,4]benzodiazepine
Para-diazepine
Fluorobenzene
Halobenzene
Aryl chloride
Aryl fluoride
Aryl halide
Monocyclic benzene moiety
Benzenoid
N-substituted imidazole
Heteroaromatic compound
Azole
Imidazole
Ketimine
Azacycle
Organic 1,3-dipolar compound
Propargyl-type 1,3-dipolar organic compound
Organofluoride
Organonitrogen compound
Organopnictogen compound
Organic nitrogen compound
Hydrocarbon derivative
Organochloride
Imine
Organohalogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

diazepine (CHEBI:6931 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	159°C
Boiling Point	Not Available
Solubility	0.024 mg/mL

Predicted Properties

Property	Value	Source
Water Solubility	0.0099 g/L	ALOGPS
logP	3.89	ALOGPS
logP	3.33	ChemAxon
logS	-4.5	ALOGPS
pKa (Strongest Basic)	6.57	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	30.18 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	99.43 m³·mol⁻¹	ChemAxon
Polarizability	32.7 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-002g-5092000000-4478c9440e5f31cecc49	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-03di-0910000000-98021a5812f1663e9397	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-0009000000-2411220f611ba30ef225	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004i-0009000000-c724b297ae99edb399d3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-004l-0098000000-b57c162c4eeaad9ef111	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0006-0090000000-a3133528f5491f4c9a6b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-05fs-0290000000-ee126555f849ecfff795	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004i-0009000000-4ae622c7b53369b0cfb1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-004i-0019000000-00c3c9e2813a454acda1	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-002f-0093000000-a8ca99ef6c84536bff07	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0006-0091000000-3edc4aa6f67d99b789a8	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0abd-0290000000-aa5e16437618ad2adb86	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-05fs-0490000000-a323090224c5b01e3990	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-004i-0189000000-6e704a4a2a65211394ab	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-03di-0910000000-98021a5812f1663e9397	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-004i-0009000000-5b177595069a22f7499c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-004i-0019000000-d4a03e7fbafc667f26cd	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-05fs-0290000000-073275db750ee5c73815	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-0006-0090000000-1c567d03f4799499290c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-002f-0093000000-77027f57247046e6973c	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004i-0019000000-75a4c3ae620bf5e6503a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-004i-0029000000-6729271ff5dbb7d43009	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a7i-1390000000-39f40fc60488c1207b28	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0009000000-b77187b6c2f47259d8d6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00di-0029000000-91cf028d658129087ce6	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0ufu-5091000000-645cab1e9777fb49b7b2	Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-03di-3839000000-42781254e15bcd5b31b6	Spectrum

Toxicity Profile

Route of Exposure

Rapidly absorbed after oral administration. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%. The absolute bioavailability, if given intramuscularly (IM), is greater than 90%. Cmax, IM = 90 ng/mL; Tmax, IM = 0.5 hours. Following IM administered, Cmax for midazolam and its 1-hydroxy metabolite were approxiately one-half of those achieved after intravenous injection.

Mechanism of Toxicity

It is thought that the actions of benzodiazepines such as midazolam are mediated through the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which is one of the major inhibitory neurotransmitters in the brain. Benzodiazepines increase the activity of GABA, thereby producing a calming effect, relaxing skeletal muscles, and inducing sleep. Benzodiazepines act as agonists at the benzodiazepine receptors, which form a component of the benzodiazepine-GABA receptor-chloride ionophore complex. Most anxiolytics appear to act through at least one component of this complex to enhance the inhibitory action of GABA.

Metabolism

Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, (alpha)-hydroxymidazolam (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (makes up 5% or less of the biotransformation products). 1-hydroxy-midazolam is at least as potent as the parent compound and may contributed to the overall activity of midazolam. In vitro studies have demonstrated that the affinities of 1- and 4-hydroxy-midazolam for the benzodiazepine receptor are approximately 20% and 7%, respectively, relative to midazolam. It also undergoes N-glucuronidation via UGT1A4. Route of Elimination: Midazolam is primarily metabolized in the liver and gut by human cytochrome P450 IIIA4 (CYP3A4) to its pharmacologic active metabolite, alpha-hydroxymidazolam, followed by glucuronidation of the alpha-hydroxyl metabolite which is present in unconjugated and conjugated forms in human plasma. The alpha- hydroxymidazolam glucuronide is then excreted in urine. No significant amount of parent drug or metabolites is extractable from urine before beta-glucuronidase and sulfatase deconjugation, indicating that the urinary metabolites are excreted mainly as conjugates. The amount of midazolam excreted unchanged in the urine when given intravenously is less than 0.5%. 45% to 57% of the dose was excreted in the urine as 1-hydroxymethyl midazolam conjugate. Half Life: Intravenous, healthy adults = 1.8 to 6.4 hours (mean of 3 hours)

Toxicity Values

LD50: 825 mg/kg (Oral, Rat)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Intravenous midazolam is indicated for procedural sedation (often in combination with an opioid, such as fentanyl), for pre-op sedation, for the induction of general anesthesia, and for sedation of ventilated patients in critical care units. Oral midazolam is indicated for the short term treatment of moderately severe insomnia in patients who did not adequately react to other hypnotics, and who have persistent trouble in falling asleep. [Wikipedia]

Minimum Risk Level

Not Available

Health Effects

They cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.

Symptoms

Not Available

Treatment

Treatment of midazolam overdosage is the same as that followed for overdosage with other benzodiazepines. Respiration, pulse rate and blood pressure should be monitored and general supportive measures should be employed. Attention should be given to the maintenance of a patent airway and support of ventilation, including administration of oxygen. Should hypotension develop, treatment may include intravenous fluid therapy, repositioning, judicious use of vasopressors appropriate to the clinical situation, if indicated, and other appropriate counter-measures. Gastrointestinal decontamination with lavage and/or activated charcoal once the patient's airway is secure is also recommended. Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of midazolam and may be used in situations when an overdose with a benzodiazepine is known or suspected. (7)

Concentrations

Not Available

External Links

DrugBank ID

DB00683

HMDB ID

HMDB0014821

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID