| Candidate ID: | R0195 |
| Source ID: | DB00683 |
| Source Type: | approved; illicit |
| Compound Type: |
small molecule
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| Compound Name: |
Midazolam
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| Synonyms: |
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| Molecular Formula: |
C18H13ClFN3
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| SMILES: |
CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12
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| Structure: |
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| DrugBank Description: |
Midazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties.[A173842] It belongs to a class of drugs called _benzodiazepines_. This drug is unique from others in this class due to its rapid onset of effects and short duration of action.[A173842] Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in various biomedical applications, including dentistry, cardiac surgery, and endoscopic procedures as pre-anesthetic medication, and as an adjunct to local anesthesia.[F2977]
This drug was initially approved by the US FDA in 1985, and has been approved for various indications since.[FDA label] In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults.[FDA label] In May 2019, the nasal spray of midazolam was approved for the acute treatment of distinctive intermittent, stereotypic seizure episodes in patients 12 years of age and older. Midazolam is considered a schedule IV drug in the United States due to the low potential for abuse and low risk of dependence.[L5074]
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| CAS Number: |
59467-70-8
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| Molecular Weight: |
325.767
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| DrugBank 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 patient’s usual seizure pattern in patients with epilepsy 12 years of age and older.[L6559]
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| DrugBank Pharmacology: |
**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]
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| DrugBank 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]
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| Targets: |
GABA-A receptor (anion channel); GABA-A receptor (benzodiazepine site); Adenosine receptor A2a
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| Inclusion Criteria: |
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