General
Preferred name
MIDAZOLAM
Synonyms
MIDAZOLAM HYDROCHLORIDE ()
MIDAZOLAM MALEATE ()
USL-261 ()
Midazolam in 0.9% sodium chloride ()
USL261 ()
Nayzilam ()
Midazolam in 0.8% sodium chloride ()
Midazolam civ ()
Midazolam ()
Rocam ()
Hypnovel ()
Seizalam ()
SHP-615 ()
Midazolam hydrochloride civ ()
Versed ()
Dormicum ()
Midazolam hcl ()
Buccolam ()
Midozalam hydrochloride ()
RO 21-3981/003 ()
Midazolam hydrochloride (autoinjector) ()
Midazolam hydrochloride preservative free ()
Ro-213981-003 ()
SHP615 ()
Ro-213981001 ()
NSC-751451 ()
RO 21-3981/001 ()
Midazolam (as maleate) ()
NSC-313452 ()
Midazolam (CRM) ()
Midazolam-d4 (maleate) (CRM) ()
P&D ID
PD009850
CAS
59467-70-8
59467-96-8
59467-94-6
Tags
natural product
drug
available
Approved by
PMDA
EMA
FDA
First approval
1985
Drug Status
illicit
approved
Drug indication
Anesthetic (injectable),Anesthetic (intravenous)
Epilepsy
Anesthetic (injectable)
Anesthetic (intravenous)
Irritability
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
**General effects** 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 benzodiazepine drugs, include sedative, anxiolytic, amnestic, muscle relaxant, as well as hypnotic activities [F2434]. Benzodiazepines enhance the inhibitory action of the amino acid neurotransmitter gamma-aminobutyric acid (GABA). Receptors for GABA are targeted by many important drugs that affect GABA function and are commonly used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, and aggressive behavior [A173854]. **Sedation and memory** The onset of sedation after intramuscular administration in adults is 15 minutes, with maximal sedation occurring 30-60 minutes after injection [FDA label]. In one study of adults, when tested the following day, 73% of the patients who were administered midazolam intramuscularly had no recollection of memory cards shown 30 minutes following drug administration; 40% had no recollection of the memory cards shown 60 minutes after drug administration. Onset time of sedative effects in pediatric patients begins within 5 minutes and peaks at 15-30 minutes depending upon the dose administered. In the pediatric population, up to 85% had no memory of pictures shown after receiving intramuscular midazolam compared to 5% of the placebo control group [F2434]. Sedation in both adult and pediatric patients is reached within 3 to 5 minutes post intravenous (IV) injection. The time of onset is affected by the dose administered and the simultaneous administration of narcotic pre-medication. Seventy-one (71%) percent of the adult patients in clinical endoscopy studies had no memory of insertion of the endoscope; 82% of the patients had no memory of withdrawal of the endoscope [FDA label]. **Anesthesia induction** When midazolam is administered intravenously (IV) for anesthetic induction, induction of anesthesia occurs in about 1.5 minutes when narcotic pre-medication has been given and in 2 to 2.5 minutes without narcotic pre-medication/ other sedative pre-medication. Impairment in a memory test was observed in 90% of the patients [FDA label].
MOA
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 central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening [F2434]. These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system [A173842].
INDICATION
The midazolam intravenous injection is indicated for preoperative sedation/anxiolysis/anesthesia induction/amnesia [F2434], and the intramuscular injection is indicated for the treatment of status epilepticus in adults [FDA label]. Midazolam is also an agent for conscious sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic, or endoscopic procedures. It is important to note that various routes may be applicable to different indications. Refer to the "indications" section of this drug entry for more detailed information.
METABOLISM
Midazolam is primarily metabolized in the liver and gut by CYP3A4 [FDA label] to its pharmacologic active metabolite, _alpha-hydroxymidazolam_ (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (which makes up 5% or less of the biotransformation products). This metabolite likely contributes to the pharmacological effects of midazolam. Midazolam also undergoes N-glucuronidation via UGT1A4 after the process of hepatic oxidation by cytochrome enzymes [A173842].
HALF-LIFE
**Intravenous**: healthy adults = 1.8 to 6.4 hours (mean of 3 hours) [F2434]. **Intramuscular**: Following IM administration of 10 mg midazolam, mean (±SD) elimination half-life was 4.2 (±1.87) hours [FDA label].
PHARMACODYNAMICS
**General effects**; ; 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 benzodiazepine drugs, include sedative, anxiolytic, amnestic, muscle relaxant, as well as hypnotic activities.[F2434] Benzodiazepines enhance the inhibitory action of the amino acid neurotransmitter gamma-aminobutyric acid (GABA). Receptors for GABA are targeted by many important drugs that affect GABA function and are commonly used in the treatment of anxiety disorder, epilepsy, insomnia, spasticity, and aggressive behavior.[A173854]; ; **Sedation and memory**; ; The onset of sedation after intramuscular administration in adults is 15 minutes, with maximal sedation occurring 30-60 minutes after injection.[FDA label] In one study of adults, when tested the following day, 73% of the patients who were administered midazolam intramuscularly had no recollection of memory cards shown 30 minutes following drug administration; 40% had no recollection of the memory cards shown 60 minutes after drug administration. Onset time of sedative effects in pediatric patients begins within 5 minutes and peaks at 15-30 minutes depending upon the dose administered. In the pediatric population, up to 85% had no memory of pictures shown after receiving intramuscular midazolam compared to 5% of the placebo control group.[F2434]; ; Sedation in both adult and pediatric patients is reached within 3 to 5 minutes post intravenous (IV) injection. The time of onset is affected by the dose administered and the simultaneous administration of narcotic pre-medication. Seventy-one (71%) percent of the adult patients in clinical endoscopy studies had no memory of insertion of the endoscope; 82% of the patients had no memory of withdrawal of the endoscope.[FDA label]; ; **Anesthesia induction**; ; When midazolam is administered intravenously (IV) for anesthetic induction, induction of anesthesia occurs in about 1.5 minutes when narcotic pre-medication has been given and in 2 to 2.5 minutes without narcotic pre-medication/ other sedative pre-medication. Impairment in a memory test was observed in 90% of the patients.[FDA label]
MOA
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 central nervous system. Benzodiazepines increase the activity of GABA, thereby producing a sedating effect, relaxing skeletal muscles, and inducing sleep, anesthesia, and amnesia. Benzodiazepines bind to the benzodiazepine site on GABA-A receptors, which potentiates the effects of GABA by increasing the frequency of chloride channel opening.[F2434] These receptors have been identified in different body tissues including the heart and skeletal muscle, although mainly appear to be present in the central nervous system.[A173842]
INDICATION
**Intravenous** ; ; Indicated for promoting preoperative sedation, anxiolysis, anesthesia induction, or amnesia.[F2434]; ; **Intramuscular** ; ; Indicated for the treatment of status epilepticus in adults.[FDA label]; ; **Nasal** ; ; Indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patientâs usual seizure pattern in patients with epilepsy 12 years of age and older.[L6559]
HALF-LIFE
**Intravenous**: healthy adults = 1.8 to 6.4 hours (mean of 3 hours).[F2434]; ; **Intramuscular**: Following IM administration of 10 mg midazolam, mean (±SD) elimination half-life was 4.2 (±1.87) hours.[FDA label]
METABOLISM
Midazolam is primarily metabolized in the liver and gut by CYP3A4 [FDA label] to its pharmacologic active metabolite, _alpha-hydroxymidazolam_ (also known as 1-hydroxy-midazolam), and 4-hydroxymidazolam (which makes up 5% or less of the biotransformation products). This metabolite likely contributes to the pharmacological effects of midazolam. Midazolam also undergoes N-glucuronidation via UGT1A4 after the process of hepatic oxidation by cytochrome enzymes.[A173842]; ;
DESCRIPTION
Midazolam is a benzodiazepine class sedative drug.
(GtoPdb)
ROE
The _α-hydroxymidazolam_ glucuronide conjugate of midazolam is excreted in urine. No significant amount of parent drug or metabolites is found in urine before beta-glucuronidase and sulfatase deconjugation, suggesting 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 [F2434]. Plasma clearance of midazolam is higher in patients that remain in supine position, because of a 40-60 percent increase in hepatic blood flow during supination. Pregnancy may also increase the metabolism of midazolam [A173842].
ABSORPTION
**Oral Absorption**: Rapidly absorbed after oral administration. The absolute bioavailability, if given intramuscularly (IM), is greater than 90% [FDA label]. Due to first pass metabolism, only 40-50% of the administered oral dose reaches the circulation [A173842]. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36% [L5092]. **Intramuscular Absorption**: The mean peak concentration (Cmax) and time to peak (Tmax) following the IM dose was 90 ng/mL (20% CV) and 0.5 hour (50% CV)[FDA label]. **Rectal administration**: After rectal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes. The absolute bioavailability is approximately 50% [F2977]. **Intranasal Administration**: Midazolam is absorbed rapidly after intranasal administration. Mean peak plasma concentrations are reached within 10.2 to 12.6 minutes. The bioavailability is between 55 and 57% [F2977].
ROE
The _α-hydroxymidazolam_ glucuronide conjugate of midazolam is excreted in urine. No significant amount of parent drug or metabolites is found in urine before beta-glucuronidase and sulfatase deconjugation, suggesting 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.[F2434]; ; Plasma clearance of midazolam is higher in patients that remain in supine position, because of a 40-60 percent increase in hepatic blood flow during supination. Pregnancy may also increase the metabolism of midazolam.[A173842]
ABSORPTION
**Oral Absorption**: Rapidly absorbed after oral administration. The absolute bioavailability, if given intramuscularly (IM), is greater than 90% [FDA label]. Due to first pass metabolism, only 40-50% of the administered oral dose reaches the circulation.[A173842] The absolute bioavailability of the midazolam syrup in pediatric patients is about 36%.[L5092]; ; **Intramuscular Absorption**: The mean peak concentration (Cmax) and time to peak (Tmax) following the IM dose was 90 ng/mL (20% CV) and 0.5 hour (50% CV).[FDA label]; ; **Rectal administration**: After rectal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes. The absolute bioavailability is approximately 50%.[F2977]; ; ; **Intranasal Administration**: Midazolam is absorbed rapidly after intranasal administration. Mean peak plasma concentrations are reached within 10.2 to 12.6 minutes. The bioavailability is between 55 and 57%.[F2977];
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
22
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Guide to Pharmacology
IPPI - DB
Ki Database
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
NPC Screening Collection
ReFrame library
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
79
Molecular Weight
325.08
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
0
Rotatable Bonds
1
Ring Count
4
Aromatic Ring Count
3
cLogP
4.32
TPSA
30.18
Fraction CSP3
0.11
Chiral centers
0.0
Largest ring
7.0
QED
0.65
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Therapeutic Class
Hypnotics and Sedatives
Source data
