Identification

Name
Midazolam
Accession Number
DB00683  (APRD00680)
Type
Small Molecule
Groups
Approved, Illicit
Description

Midazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties [6]. 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 [6]. Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in dentistry, cardiac surgery, endoscopic procedures, as pre-anesthetic medication, and as an adjunct to local anesthesia [12].

In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults [Label]. Midazolam is considered a schedule IV drug in the United States. This category is defined by drugs, substances, or chemicals with a low potential for abuse and low risk of dependence [9]. This drug was initially approved by the US FDA in 1985, and has been approved for various indications since [Label].

Structure
Thumb
Synonyms
  • Midazolam
  • Midazolamum
External IDs
Dea No. 2884 / Ro 21-3981/001 / Ro 21-3981/003
Product Ingredients
IngredientUNIICASInChI Key
Midazolam hydrochlorideW7TTW573JJ59467-96-8PLYSCVSCYOQVRP-UHFFFAOYSA-N
Midazolam maleate77520S18SE59467-94-6XYGVIBXOJOOCFR-BTJKTKAUSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BuccolamSolution7.5 mgBuccalShire Services Bvba2011-09-05Not applicableEu
BuccolamSolution5 mgBuccalShire Services Bvba2011-09-05Not applicableEu
BuccolamSolution2.5 mgBuccalShire Services Bvba2011-09-05Not applicableEu
BuccolamSolution10 mgBuccalShire Services Bvba2011-09-05Not applicableEu
Midazolam InjectionSolution1 mgIntramuscular; IntravenousFresenius Kabi2001-03-26Not applicableCanada
Midazolam InjectionSolution1 mgIntramuscular; IntravenousSandoz Canada Incorporated1999-07-21Not applicableCanada
Midazolam InjectionSolution1 mgIntramuscular; IntravenousNovopharm Limited2001-12-17Not applicableCanada
Midazolam InjectionLiquid5 mgIntramuscular; IntravenousFresenius Kabi2001-03-26Not applicableCanada
Midazolam InjectionSolution5 mgIntramuscular; IntravenousMylan PharmaceuticalsNot applicableNot applicableCanada
Midazolam InjectionSolution5 mgIntramuscular; IntravenousPfizer2015-03-31Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-midazolam Injectable 1 mg/mlLiquid1 mgIntramuscular; IntravenousApotex Corporation2001-04-102013-08-02Canada
Apo-midazolam Injectable 5 mg/mlLiquid5 mgIntramuscular; IntravenousApotex Corporation2001-04-102013-08-02Canada
MidazolamInjection5 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.2000-06-20Not applicableUs
MidazolamInjection5 mg/1mLIntramuscular; IntravenousCardinal Health2000-06-202016-09-30Us
MidazolamInjection1 mg/1mLIntramuscular; IntravenousCardinal Health2000-06-202015-08-31Us
MidazolamInjection, solution1 mg/1mLIntramuscular; IntravenousThe Medicines Company2000-07-14Not applicableUs
MidazolamInjection, solution5 mg/1mLIntramuscular; IntravenousAthenex Pharmaceutical Division, Llc.2016-12-14Not applicableUs
MidazolamInjection, solution5 mg/1mLIntramuscular; IntravenousSagent Pharmaceuticals2012-03-192018-05-01Us
MidazolamInjection5 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.2000-06-20Not applicableUs
MidazolamInjection, solution5 mg/1mLIntramuscular; IntravenousFresenius Kabi2014-10-03Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Midazolam HClMidazolam hydrochloride (0.5 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2014-09-03Not applicableUs
Midazolam HClMidazolam hydrochloride (1 mg/1mL)Injection, solutionIntravenousCantrell Drug Company2013-06-28Not applicableUs
MKO MeltMidazolam (3 mg/1) + Ketamine hydrochloride (25 mg/1) + Ondansetron hydrochloride dihydrate (2 mg/1)TrocheSublingualImprimis Njof, Llc2018-12-01Not applicableUs
International/Other Brands
Anquil (General Pharma) / Benzosed (Pharmaceutical) / Buccolam / Dalam (Richmond) / Damizol (Specifar) / Demizolam (Dem Ilaç) / Doricum (Roche) / Dormicum (Roche) / Dormid (Scott) / Dormipron (Chalver) / Dormire (Cristália) / Dormitol (Square) / Dormixal (Demo) / Dormonid (Roche) / Drimnorth (Northia) / Epistatus (IFET) / Flormidal (Galenika) / Fulsed (Ranbaxy) / Fulsed Injection (Terapia) / Garen (Bio-Pharma) / Gobbizolam (Gobbi) / Hipnazolam (EMS) / Hipnoz (Pharos) / Hypnofast (Incepta) / Hypnovel (Roche) / Ipnovel (Roche) / Nocturna (Lafi) / Setam (Rimsa) / Talentum (Fisiopharma) / Terap (Sanitas) / Versed (Roche)
Categories
UNII
R60L0SM5BC
CAS number
59467-70-8
Weight
Average: 325.767
Monoisotopic: 325.078203343
Chemical Formula
C18H13ClFN3
InChI Key
DDLIGBOFAVUZHB-UHFFFAOYSA-N
InChI
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
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
SMILES
CC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12

Pharmacology

Indication

The midazolam intravenous injection is indicated for preoperative sedation/anxiolysis/anesthesia induction/amnesia [11], and the intramuscular injection is indicated for the treatment of status epilepticus in adults [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.

Associated Conditions
Associated Therapies
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 [11]. 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 [7].

Sedation and memory

The onset of sedation after intramuscular administration in adults is 15 minutes, with maximal sedation occurring 30-60 minutes after injection [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 [11].

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 [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 [Label].

Mechanism of action

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 [11]. 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 [6].

TargetActionsOrganism
AGamma-aminobutyric acid receptor subunit alpha-1
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-2
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-5
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-3
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-4
potentiator
Humans
AGamma-aminobutyric acid receptor subunit alpha-6
potentiator
Humans
Absorption

Oral Absorption: Rapidly absorbed after oral administration. The absolute bioavailability, if given intramuscularly (IM), is greater than 90% [Label]. Due to first pass metabolism, only 40-50% of the administered oral dose reaches the circulation [6]. The absolute bioavailability of the midazolam syrup in pediatric patients is about 36% [10].

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)[Label].

Rectal administration: After rectal administration midazolam is absorbed rapidly. Maximum plasma concentration is reached within 30 minutes. The absolute bioavailability is approximately 50% [12].

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% [12].

Volume of distribution

Female gender, old age, and obesity may increase the volume of distribution. Midazolam may also cross the placenta and has been detected in human milk and cerebrospinal fluid [Label], [11].

Intravenous administration

1.24 to 2.02 L/kg [pediatric patients (6 months to <16 years) receiving 0.15 mg/kg IV midazolam] 1 to 3.1 L/kg [midazolam intravenously administered, healthy adults] [11].

Intramuscular administration

The mean apparent volume of distribution of midazolam after a single IM dose of 10 mg midazolam in healthy adults was 2117 (±845.1) mL/kg [Label].

Protein binding

Midazolam is approximately 97% bound to plasma protein, mainly albumin, in adults. The 1-hydroxy metabolite is approximately 89% bound to plasma protein[11].

Metabolism

Midazolam is primarily metabolized in the liver and gut by CYP3A4 [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 [6].

Route of elimination

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 [11].

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 [6].

Half life

Intravenous: healthy adults = 1.8 to 6.4 hours (mean of 3 hours) [11].

Intramuscular: Following IM administration of 10 mg midazolam, mean (±SD) elimination half-life was 4.2 (±1.87) hours [Label].

Clearance

Intramuscular: apparent total body clearance, 367.3 (±73.5) mL/hr/kg [Label]. Intravenous: total clearance (Cl), 0.25 to 0.54 L/hr/kg

Toxicity

LD50=215 mg/kg, in rats [MSDS].

Overdose

Signs of overdose include sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma, and deleterious effects on vital signs. Serious cardiorespiratory adverse reactions have occurred, sometimes ending in death or permanent neurologic effects, after the administration of midazolam [Label].

A note on cardiac and respiratory depression

After administration of midazolam, continuous monitoring of respiratory and cardiac function is recommended until the patient is in stable condition. Serious and life-threatening cardiorespiratory adverse reactions, including hypoventilation, airway obstruction, apnea, and hypotension have been reported with the use of midazolam. Patients should be monitored in a setting with immediate access to resuscitative drugs if they are required. Resuscitation equipment and personnel trained in their use and skilled in airway management should be available when midazolam is administered [Label].

The usual recommended intramuscular pre-medicating doses of midazolam do not depress the ventilatory response to carbon dioxide stimulation to a clinically significant extent in adults. Intravenous induction doses of midazolam depress the ventilatory response to carbon dioxide stimulation for at least 15 minutes longer than the duration of ventilatory depression following administration of thiopental in adults. Impairment of ventilatory response to carbon dioxide is more severe in adult patients diagnosed with chronic obstructive pulmonary disease (COPD) [11].

A note on dependence

When midazolam is used in long-term sedation in the ICU (intensive care unit) or other settings, physical dependence on midazolam may develop. The risk of dependence increases with dose and duration of treatment; this risk is also greater in patients with a medical history of substance abuse [9].

Special caution should be exercised when administering midazolam in the following populations [9]: adults over 60 years of age, chronically ill or debilitated patients, which may include patients with chronic respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function, pediatric patients (especially those with cardiovascular instability). These high-risk patients require lower dosages and should be monitored on a continuous basis for early signs of alterations of vital functions, so that appropriate management may be administered.

Mutagenesis

Midazolam was negative for genotoxicity during in vitro and in vivo assays [Label].

Impairment of Fertility

When midazolam (0, 1, 4, or 16 mg/kg) was given orally to male and female rats before and during mating and continuing in females throughout gestation and lactation, no adverse effects on male or female fertility were observed. Midazolam plasma exposures (AUC) at the highest dose tested were approximately 6 times that in humans at the recomended human dose [Label].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Midazolam can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Midazolam can be decreased when combined with (S)-Warfarin.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Midazolam can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Midazolam is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of Midazolam can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Midazolam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Midazolam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Midazolam is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of Midazolam can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe serum concentration of Midazolam can be increased when it is combined with 6-Deoxyerythronolide B.
Food Interactions
  • Grapefruit juice slows the product's absorption and significantly increases its bioavailability.

References

Synthesis Reference
US6262260
General References
  1. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [PubMed:6135616]
  2. Isojarvi JI, Tokola RA: Benzodiazepines in the treatment of epilepsy in people with intellectual disability. J Intellect Disabil Res. 1998 Dec;42 Suppl 1:80-92. [PubMed:10030438]
  3. Garratt JC, Gent JP, Feely M, Haigh JR: Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential? Eur J Pharmacol. 1988 Jan 5;145(1):75-80. [PubMed:2894998]
  4. Tokunaga S, Takeda Y, Shinomiya K, Hirase M, Kamei C: Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats. J Pharmacol Sci. 2007 Feb;103(2):201-6. Epub 2007 Feb 8. [PubMed:17287588]
  5. Vermeeren A: Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs. 2004;18(5):297-328. [PubMed:15089115]
  6. Nordt SP, Clark RF: Midazolam: a review of therapeutic uses and toxicity. J Emerg Med. 1997 May-Jun;15(3):357-65. [PubMed:9258787]
  7. Jembrek MJ, Vlainic J: GABA Receptors: Pharmacological Potential and Pitfalls. Curr Pharm Des. 2015;21(34):4943-59. [PubMed:26365137]
  8. Siegel GJ, Agranoff BW, Albers RW et al. (1999). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (6th ed.). Lippincott Williams.
  9. Drug Scheduling: United States Drug Enforcement Administration (DEA) [Link]
  10. DailyMed: Midazolam [Link]
  11. Intravenous Midazolam FDA label [File]
  12. MedSafe NZ: Midazolam Inj [File]
External Links
Human Metabolome Database
HMDB0014821
KEGG Drug
D00550
KEGG Compound
C07524
PubChem Compound
4192
PubChem Substance
46507611
BindingDB
21363
ChEBI
6931
ChEMBL
CHEMBL655
Therapeutic Targets Database
DAP000241
PharmGKB
PA450496
IUPHAR
3342
Guide to Pharmacology
GtP Drug Page
HET
08J
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Midazolam
ATC Codes
N05CD08 — Midazolam
AHFS Codes
  • 28:24.08 — Benzodiazepines
PDB Entries
3u5k / 5te8
FDA label
Download (250 KB)
MSDS
Download (68.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionDepression1
0CompletedTreatmentAnxiety Disease1
0CompletedTreatmentBipolar I Disorder / Bipolar II Disorder / Depression, Bipolar / Major Depressive Disorder (MDD) / Suicidal Thoughts1
0RecruitingBasic ScienceInteraction Drug Food1
0RecruitingTreatmentMidazolam Overdose1
0RecruitingTreatmentSedation, Conscious1
0SuspendedTreatmentKetamine / Malignancies / Tiredness1
1Active Not RecruitingBasic ScienceHealthy Volunteers1
1Active Not RecruitingBasic ScienceNash1
1Active Not RecruitingBasic ScienceNeoplasms Metastasis1
1Active Not RecruitingOtherBiological Availability1
1Active Not RecruitingOtherHealthy Volunteers1
1Active Not RecruitingOtherNeoplasms1
1Active Not RecruitingTreatmentAdvanced Non-Central Nervous System (CNS) Malignancies1
1Active Not RecruitingTreatmentCancer of the Ovary / Carcinoid tumour of the gastrointestinal tract / Colorectal Cancers / Head and Neck Carcinoma / Islet Cell Tumor / Lung Cancers / Metastatic Cancers / Neuroendocrine Carcinoma of the Skin / Pheochromocytomas / Sarcomas / Unspecified Adult Solid Tumor, Protocol Specific1
1Active Not RecruitingTreatmentDrug Interaction Potential1
1Active Not RecruitingTreatmentEpidermal Growth Factor Receptor Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL) / Non-Hodgkin's Lymphoma, Solid Cancers / Solid Cancers1
1Active Not RecruitingTreatmentTumors, Solid1
1CompletedNot AvailableHealthy Volunteers9
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of ASP015K and Midazolam1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Isavuconazole / Pharmacokinetics of Midazolam1
1CompletedNot AvailableHepatitis C Viral Infection1
1CompletedNot AvailableHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedNot AvailablePain, Chronic1
1CompletedNot AvailablePharmacokinetic Interactions1
1CompletedNot AvailableSchizophrenia Patients1
1CompletedBasic ScienceAlzheimer's Disease (AD) / Metabolism1
1CompletedBasic ScienceAtopic Dermatitis (AD)1
1CompletedBasic ScienceDiabetes Mellitus (DM) / Glucose Metabolism Disorders / Type 2 Diabetes Mellitus1
1CompletedBasic ScienceDrug Biotransformation / Membrane Transport1
1CompletedBasic ScienceDrug Drug Interaction (DDI)1
1CompletedBasic ScienceEndometriosis1
1CompletedBasic ScienceGenotype-related Drug Metabolism1
1CompletedBasic ScienceHealthy Adult Subjects and Healthy Elderly Subjects1
1CompletedBasic ScienceHealthy Adult Volunteers1
1CompletedBasic ScienceHealthy Male Volunteers1
1CompletedBasic ScienceHealthy Participants1
1CompletedBasic ScienceHealthy Volunteers16
1CompletedBasic ScienceHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedBasic ScienceHealthy Volunteers / Pharmacologic Actions1
1CompletedBasic ScienceModerate to Severe Plaque Psoriasis1
1CompletedBasic SciencePharmacokinetic Assessments in Healthy Volunteers1
1CompletedBasic ScienceRheumatoid Arthritis3
1CompletedBasic ScienceType 2 Diabetes Mellitus1
1CompletedBasic ScienceVA Drug Interactions / VA Drug Interactions [VA Drug Interaction]1
1CompletedDiagnosticCytochrome / Pharmacokinetics1
1CompletedDiagnosticDigestive System Disorders1
1CompletedDiagnosticDrug Drug Interaction (DDI)1
1CompletedDiagnosticHealthy Volunteers2
1CompletedHealth Services ResearchHealthy Volunteers1
1CompletedOtherALK-positive Advanced Tumors1
1CompletedOtherAdvanced Solid Tumors1
1CompletedOtherDrug Drug Interaction (DDI) / Healthy Volunteers1
1CompletedOtherHealthy Volunteers5
1CompletedOtherHealthy Volunteers / Rheumatoid Arthritis1
1CompletedOtherLeukemia, Lymphocytic, Chronic, B-Cell1
1CompletedOtherPhase 11
1CompletedOtherProstatic Neoplasms1
1CompletedOtherTumors, Solid1
1CompletedTreatmentAcute Myocardial Infarction (AMI) / Pain NOS1
1CompletedTreatmentAdult Solid Neoplasm1
1CompletedTreatmentAdvanced Solid Tumors, Excluding Breast Cancer1
1CompletedTreatmentAmnesia-Memory Loss / Memory Losses1
1CompletedTreatmentAnemias / Healthy Volunteers1
1CompletedTreatmentAtherosclerosis1
1CompletedTreatmentBack Pain Lower Back1
1CompletedTreatmentBacterial Infections / Pneumonia / Skin Diseases, Infectious1
1CompletedTreatmentCarcinoma NOS / Hodgkins Disease (HD) / Lymphoma, Large-Cell, Anaplastic / Neoplasms / Non-Hodgkin's Lymphoma (NHL)1
1CompletedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pharmacokinetics of MDV31001
1CompletedTreatmentChemotherapy-Induced Nausea and Vomiting (CINV) / Post-Operative Nausea and Vomiting (PONV)1
1CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
1CompletedTreatmentCrohn's Disease (CD)1
1CompletedTreatmentDepressive Disorders / Healthy Volunteers1
1CompletedTreatmentDrug Drug Interaction (DDI)3
1CompletedTreatmentDrug Interaction Potentiation3
1CompletedTreatmentDrug reactions1
1CompletedTreatmentHealthy Male Volunteers1
1CompletedTreatmentHealthy Volunteers26
1CompletedTreatmentHealthy Volunteers / Psoriasis1
1CompletedTreatmentHeart Failure, Unspecified1
1CompletedTreatmentHeathy Volunteer1
1CompletedTreatmentImpaired Renal Function1
1CompletedTreatmentInfectious Diseases1
1CompletedTreatmentInfluenza in Humans1
1CompletedTreatmentJapanese Healthy Adult Males1
1CompletedTreatmentMalignancies1
1CompletedTreatmentMalignancies / Neoplasms, Breast1
1CompletedTreatmentNeoplasms1
1CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
1CompletedTreatmentPsoriasis2
1CompletedTreatmentPulmonary Tuberculosis (TB) / Tuberculosis Infection2
1CompletedTreatmentRelapsed or Refractory Advanced Cancer1
1CompletedTreatmentSchizophrenia or Schizoaffective Disorder1
1CompletedTreatmentSeizures1
1CompletedTreatmentSkin Diseases, Bacterial1
1CompletedTreatmentTuberculosis Infection1
1CompletedTreatmentTumors1
1CompletedTreatmentTumors, Solid2
1CompletedTreatmentType 2 Diabetes Mellitus2
1CompletedTreatmentCMET-dysregulated Advanced Solid Tumors1
1Not Yet RecruitingOtherCarcinoma, Advanced ALK+ or ROS1+Non-Small-Cell Lung, Neoplasm, Advanced ALK+ or ROS1+Solid Tumors1
1Not Yet RecruitingOtherHealthy Volunteers1
1Not Yet RecruitingPreventionCesarean Section Complications1
1RecruitingBasic ScienceHealthy Volunteers2
1RecruitingOtherCrohn's Disease (CD)1
1RecruitingOtherDepression, Bipolar / Major Depressive Episode / Unipolar Depression1
1RecruitingOtherHealthy Volunteers1
1RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
1RecruitingTreatmentAtopic Dermatitis (AD)1
1RecruitingTreatmentCancer, Advanced / Colorectal Cancers / Metastatic Melanoma / Metastatic Non-Small Cell Lung Cancer / Metastatic Pancreatic Ductal Adenocarcinoma1
1RecruitingTreatmentCancer, Advanced / Lung Cancer Non-Small Cell Cancer (NSCLC) / Mesothelioma, Malignant / Metastatic Breast Cancer (MBC) / Metastatic Cancers / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentHealthy Volunteers2
1RecruitingTreatmentHepatitis B Chronic Infection1
1RecruitingTreatmentInfections, Respiratory Syncytial Virus1
1TerminatedBasic ScienceCancer, Advanced1
1TerminatedOtherDepression / Depressive Disorder, Recurrent / Major Depressive Disorder (MDD) / Relapses1
1TerminatedOtherHealthy Volunteers3
1TerminatedOtherPsoriasis Vulgaris (Plaque Psoriasis)1
1TerminatedTreatmentCervical Pain1
1TerminatedTreatmentEpilepsies1
1TerminatedTreatmentHealthy Volunteers1
1WithdrawnTreatmentHealthy Volunteers2
1, 2Active Not RecruitingTreatmentBipolar Disorder (BD) / Major Depressive Episode / Suicidal Thoughts1
1, 2CompletedPreventionPost Operative Pain1
1, 2CompletedTreatmentShock, Septic1
1, 2Not Yet RecruitingBasic ScienceTobacco Use Disorders1
1, 2Not Yet RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentCoughing1
1, 2RecruitingTreatmentDisseminated Sclerosis / Tiredness1
1, 2TerminatedPreventionSepsis1
1, 2TerminatedTreatmentDependence, Cocaine1
1, 2TerminatedTreatmentObsessive Compulsive Disorder (OCD)1
2Active Not RecruitingTreatmentMajor depressive disorder, recurrent episode1
2Active Not RecruitingTreatmentObsessive Compulsive Disorder (OCD)1
2CompletedPreventionForearm Surgeries1
2CompletedSupportive CareChildren1
2CompletedSupportive CareDental Anxiety1
2CompletedTreatmentAnxiety Disorders / Depression / Post Traumatic Stress Disorder (PTSD)1
2CompletedTreatmentChildren Requiring Sedation to Facilitate Laceration Repair1
2CompletedTreatmentEndoscopy / Procedural Sedation1
2CompletedTreatmentMajor Depressive Disorder (MDD) / Treatment Resistant Depression (TRD)1
2CompletedTreatmentPain NOS1
2CompletedTreatmentSeizures1
2CompletedTreatmentTreatment Resistant Depression (TRD)1
2Not Yet RecruitingTreatmentMajor Depressive Episode1
2RecruitingDiagnosticDelayed Recovery From Anaesthesia1
2RecruitingPreventionSedation During Spinal Anesthesia1
2RecruitingSupportive CareCancer of the Breast / Cancer, Breast / Malignant Neoplasm of Female Breast1
2RecruitingTreatmentAdministration and Dosage of Ketamine / Endoscopic Sedation1
2RecruitingTreatmentBipolar Disorder (BD)1
2RecruitingTreatmentBorderline Personality Disorder (BPD)1
2RecruitingTreatmentKetamine / Violent Aggressive Behavior1
2RecruitingTreatmentMajor Depressive Disorder (MDD)1
2RecruitingTreatmentObsessive Compulsive Disorder (OCD)1
2RecruitingTreatmentPosttraumatic Stress Disorders1
2RecruitingTreatmentSubarachnoid Haemorrhage (SAH)1
2TerminatedTreatmentFeeling Anxious / Pain NOS1
2Unknown StatusPreventionAdenoidectomy / Otorhinolaryngologic Surgical Procedures / Postoperative Care / Postoperative pain / Surgical Procedures, Operative / Tonsillectomy1
2Unknown StatusSupportive CareIntracranial Hemorrhages / Ischemia, Brain / Strokes / Vasospasm, Intracranial1
2Unknown StatusTreatmentPost Dural Puncture Headache1
2WithdrawnDiagnosticComputerized tomography / Procedural Sedation / Traumatic Brain Injury (TBI)1
2WithdrawnSupportive CareDelirium / Dyspnea / Nausea / Pain Intractable1
2, 3CompletedPreventionDiagnostic Esophagogastroduodenoscopy1
2, 3CompletedTreatmentAnaesthesia therapy1
2, 3CompletedTreatmentAnalgesia, Patient-Controlled / Spinal Stenosis1
2, 3CompletedTreatmentBurning Nose1
2, 3CompletedTreatmentChronic Otitis Media1
2, 3CompletedTreatmentColonoscopy / Colorectal Polyps1
2, 3CompletedTreatmentCritical Illness1
2, 3CompletedTreatmentDental Anxiety / Impacted Third Molar Tooth1
2, 3CompletedTreatmentMajor depressive disorder, recurrent episode1
2, 3CompletedTreatmentPostoperative pain1
2, 3CompletedTreatmentSedation therapy1
2, 3Not Yet RecruitingTreatmentAcute Ischemic Stroke (AIS)1
2, 3Not Yet RecruitingTreatmentDepression / Pain, Acute1
2, 3Not Yet RecruitingTreatmentTreatment Resistant Depression (TRD)1
2, 3RecruitingTreatmentAnalgesia, Postoperative1
2, 3RecruitingTreatmentFeeling Anxious / Post-Operative Nausea and Vomiting (PONV) / Postoperative pain1
2, 3RecruitingTreatmentPost Traumatic Stress Disorder (PTSD)1
2, 3WithdrawnTreatmentPost Traumatic Stress Disorder (PTSD)1
3CompletedNot AvailableChronic Renal Failure (CRF) / Hip Fractures1
3CompletedDiagnosticCancer, Breast1
3CompletedPreventionEmergence Delirium1
3CompletedPreventionHigh Blood Pressure (Hypertension)1
3CompletedPreventionPost-operative Pain for Total Knee Arthroplasty1
3CompletedSupportive CareColonoscopy1
3CompletedSupportive CareEpilepsies / Hydrocephaly1
3CompletedTreatmentAcute Traumatic Pain1
3CompletedTreatmentAnaesthesia therapy1
3CompletedTreatmentBronchoscopy1
3CompletedTreatmentChild's Anxiety / Parental/Caregiver Anxiety1
3CompletedTreatmentColonoscopy1
3CompletedTreatmentContinuous Sedation in Initially Sedated Adults in ICU1
3CompletedTreatmentDental Anxiety1
3CompletedTreatmentFracture Bone1
3CompletedTreatmentPaediatric Outpatient Surgery1
3CompletedTreatmentPediatric Status Epilepticus1
3CompletedTreatmentSedation therapy1
3Not Yet RecruitingTreatmentAnaesthesia therapy / Shock, Septic1
3RecruitingSupportive CareFluoride Poisoning / Hepatic Function / Poisoning by Inhaled Anaesthetic / Recovery From Sedation / Renal Function1
3RecruitingTreatmentBreech Presentation1
3RecruitingTreatmentFeeling Anxious / Peripheral Nerve Blocks1
3RecruitingTreatmentInflammatory Reaction / Neurocostal neuralgia / Pain, Chronic1
3RecruitingTreatmentInguinal Hernias / Local Anesthesia / Sedation, Conscious1
3RecruitingTreatmentLiver Cirrhosis1
3RecruitingTreatmentTreatment Resistant Depressive Disorder1
3TerminatedTreatmentAcute Agitated Patients1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentEpilepsies1
3TerminatedTreatmentSedation in Intensive Care1
3TerminatedTreatmentTraumatic Brain Injury (TBI)1
3Unknown StatusSupportive CareSedation therapy1
3Unknown StatusTreatmentIntubation Complications1
4Active Not RecruitingSupportive CareEpilepsies / Metabolic Diseases / Traumas1
4Active Not RecruitingSupportive CareFeeling Anxious / Laceration1
4Active Not RecruitingTreatmentAcute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS) / Critical Illness / Sleep1
4Active Not RecruitingTreatmentAnxiety Disorders / Major Depressive Disorder (MDD)1
4Active Not RecruitingTreatmentDriving Performance After Minor Ambulatory Surgery / Minor Surgical Procedures With Monitored Anesthesia Care1
4Active Not RecruitingTreatmentEffect of Sedation on Heart Rate Variability1
4CompletedNot AvailableDisorders of Gallbladder, Biliary Tract and Pancrease1
4CompletedNot AvailableFailed Moderate Sedation During Procedure1
4CompletedBasic ScienceAnalgesic Drugs / Antinociceptive Agents1
4CompletedBasic SciencePharmacokinetics1
4CompletedBasic ScienceRejection, Transplant1
4CompletedDiagnosticAlteration of Cognitive Function / Gastrointestinal Dysfunction1
4CompletedOtherAnaesthesia therapy / Colonoscopy1
4CompletedPreventionAdenotonsillectomy1
4CompletedPreventionAdrenocortical Deficiency / Hemodynamics Instability1
4CompletedPreventionCognitive Impairments1
4CompletedPreventionDelirium1
4CompletedPreventionDelirium on Emergence / Inhalational Anesthetics Adverse Reaction / Strabismus Following Ocular Surgery1
4CompletedPreventionDisease, Chronic1
4CompletedPreventionElective Orthopedic Surgery1
4CompletedPreventionEmergence Agitation1
4CompletedPreventionPatients Undergoing Puncture of the Bone Marrow1
4CompletedPreventionPremedication1
4CompletedSupportive CareAnesthesia; Reaction1
4CompletedSupportive CareEndoscopy1
4CompletedSupportive CareHypothermia1
4CompletedSupportive CareInfertilities1
4CompletedSupportive CareIntubation; Difficult1
4CompletedSupportive CareIrritable Bowel Syndrome (IBS) / Malignant Neoplasm of Colon / Polyps1
4CompletedTreatmentAbscesses / Pain NOS1
4CompletedTreatmentAcute Respiratory Distress Syndrome (ARDS)1
4CompletedTreatmentAggressive Behavior / Depression / Feeling Anxious / Postoperative Period / Tiredness1
4CompletedTreatmentAnaesthesia / Premedication1
4CompletedTreatmentBrain Diseases1
4CompletedTreatmentBronchoscopy1
4CompletedTreatmentCataracts / Phacoemulsification1
4CompletedTreatmentChild Behavior / Conscious Sedation Failure During Procedure / Dental Decay1
4CompletedTreatmentChild Behavior / Dental Decay1
4CompletedTreatmentCholangiocarcinomas / Choledocholithiasis / Malignant Neoplasm of Pancreas / Pancreatitis1
4CompletedTreatmentColonoscopy / Sedation, Conscious1
4CompletedTreatmentComplications1
4CompletedTreatmentConscious Sedation Failure During Procedure1
4CompletedTreatmentCoronary Artery Disease1
4CompletedTreatmentDiagnostic Colonoscopy Screening1
4CompletedTreatmentDrug Safety / Procedural Sedation1
4CompletedTreatmentEarly Childhood Caries1
4CompletedTreatmentEfficacy and Safety of Mivacurium Chloride for Pediatric Patients1
4CompletedTreatmentEndoscopy1
4CompletedTreatmentEndoscopy, Gastrointestinal / Moderate Sedation / Propofol / Target Controlled Infusion (TCI)1
4CompletedTreatmentEndoscopy / Inflammatory Bowel Diseases (IBD) / Sedation therapy1
4CompletedTreatmentEndoscopy / Sedation therapy1
4CompletedTreatmentFailed Moderate Sedation During Procedure1
4CompletedTreatmentFailed Moderate Sedation During Procedure / Minimally Conscious State1
4CompletedTreatmentFeeling Anxious3
4CompletedTreatmentFeeling Anxious / Hepatitis, Chronic / Liver Cirrhosis1
4CompletedTreatmentFeeling Anxious / Laceration1
4CompletedTreatmentFeeling Anxious / Nausea / Pain NOS1
4CompletedTreatmentCaudal epidural block therapy / Forearm Injuries / Orthopedic Procedures / Traumas / Upper Extremity1
4CompletedTreatmentGastrointestinal Stroma Tumors / Lung Cancer Non-Small Cell Cancer (NSCLC) / Renal-cell Cancer1
4CompletedTreatmentHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
4CompletedTreatmentHernia1
4CompletedTreatmentInadequate or Impaired Respiratory Function / Pain NOS1
4CompletedTreatmentIntraoperative Analgesic Use / Postcraniotomy Headache / Postoperative Analgesic Use / Postoperative Complications1
4CompletedTreatmentKetamine Induced Agitation1
4CompletedTreatmentLung Cancers1
4CompletedTreatmentComputerized tomography / MRI of liver / Ultrasound1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4CompletedTreatmentMajor Depressive Disorder (MDD) / Suicidal Thoughts1
4CompletedTreatmentMechanically Ventilated and Intubated Subjects1
4CompletedTreatmentOsteoarthritis (OA)1
4CompletedTreatmentOther Surgical Procedures1
4CompletedTreatmentOxidative Stress / Sedation therapy1
4CompletedTreatmentProcedural Sedation1
4CompletedTreatmentProstate Cancer1
4CompletedTreatmentSedation therapy3
4CompletedTreatmentSedation, Conscious1
4CompletedTreatmentSepsis / Shock, Septic / Systemic Inflammatory Response Syndrome (SIRS)1
4CompletedTreatmentSleep Quality of Patients Undergoing TURP1
4CompletedTreatmentSuicidal Thoughts1
4CompletedTreatmentTerminal Cancer1
4Enrolling by InvitationTreatmentAnesthesia Complication / Hemodynamics Instability / Ileus paralytic / Nausea / Postoperative pain / Vomiting1
4Enrolling by InvitationTreatmentComplications / Delirium / Ventilations, Mechanical1
4Not Yet RecruitingNot AvailableChildren / Dormicum / Sedation, Conscious1
4Not Yet RecruitingHealth Services ResearchPatients Satisfaction1
4Not Yet RecruitingPreventionCritical Illness1
4Not Yet RecruitingPreventionInhalation Anesthesia1
4Not Yet RecruitingSupportive CareBronchoscopy1
4Not Yet RecruitingTreatmentAcute Pulmonary Edema1
4Not Yet RecruitingTreatmentEmergency / Procedural anxiety1
4Not Yet RecruitingTreatmentPostoperative pain1
4Not Yet RecruitingTreatmentPreanesthetic Medication1
4Not Yet RecruitingTreatmentSafety and Efficacy of Intranasal Dexmedetomidine1
4RecruitingBasic ScienceSevere Sepsis1
4RecruitingBasic ScienceType 2 Diabetes Mellitus1
4RecruitingDiagnosticCopeptin / Preanesthetic Medication1
4RecruitingDiagnosticLiver Diseases1
4RecruitingHealth Services ResearchGeneral Surgery / Sedation therapy1
4RecruitingOtherAnaesthesia therapy1
4RecruitingOtherLumbar Punctures / Minor Incision Drainage of Abscesses Not Requiring Extensive Debridement / Sedation, Conscious / Simple Lacerations Less Than 4 cm1
4RecruitingTreatmentAcute Agitation, Behavioural Emergency1
4RecruitingTreatmentAnalgesia, Postoperative1
4RecruitingTreatmentBladder Tumors / Postoperative Cognitive Dysfunction1
4RecruitingTreatmentCritical Illness / Deep Sedation / Ventilators, Mechanical1
4RecruitingTreatmentCrohn's Disease (CD) / Ulcerative Colitis (UC)1
4RecruitingTreatmentDexmedetomidine / Mechanically Ventilated Sedated Patients / Midazolam / Sedation therapy / Ventilations, Mechanical1
4RecruitingTreatmentFeeling Anxious / Pediatric ALL / Procedural anxiety1
4RecruitingTreatmentFlexible Bronchoscopy / Safety / Satisfaction / Sedation therapy1
4RecruitingTreatmentKnee Injuries1
4RecruitingTreatmentLaceration of Skin1
4RecruitingTreatmentPatients Requiring Diagnostic Gastroscopy Suitable for Sedation / Patients Requiring Diagnostic Gastroscopy With Sedation1
4RecruitingTreatmentSedation in Intensive Care Unit Patients1
4RecruitingTreatmentSedation therapy1
4RecruitingTreatmentSeizures1
4RecruitingTreatmentShock, Septic1
4TerminatedTreatmentAnaesthesia therapy1
4TerminatedTreatmentCritical Illness / Ventilations, Mechanical1
4TerminatedTreatmentFeeling Anxious1
4TerminatedTreatmentOrthopedic Procedures / Procedural Sedation / Regional Anesthesia Block1
4TerminatedTreatmentTraumatic Brain Injury (TBI)1
4Unknown StatusNot AvailableObesity, Morbid1
4Unknown StatusBasic ScienceHyperalgesia4
4Unknown StatusPreventionAnaesthetic Preconditioning / Myocardial Injury1
4Unknown StatusPreventionDelirium1
4Unknown StatusPreventionSedative Withdrawal Delirium1
4Unknown StatusTreatmentAnaesthesia therapy / Hemodynamics / Oxidative Stress1
4Unknown StatusTreatmentAnalgesia, Patient-Controlled / Arthroplasty / Gastric Resection1
4Unknown StatusTreatmentCongenital Choledochal Cyst / Congenital Hydronephrosis / Fracture Bone1
4Unknown StatusTreatmentConscious Sedation Failure During Procedure1
4Unknown StatusTreatmentDelirium1
4Unknown StatusTreatmentDexmedetomidine / Mechanically Ventilated Patients / Midazolam / Sedation therapy1
4Unknown StatusTreatmentEmergency1
4Unknown StatusTreatmentFailed Conscious Sedation During Procedure1
4Unknown StatusTreatmentHepatic Encephalopathy1
4Unknown StatusTreatmentInflammatory Disorder of Immune System / Sepsis1
4Unknown StatusTreatmentLaceration1
4Unknown StatusTreatmentLaryngoscopy / Preanesthetic Medication1
4Unknown StatusTreatmentLiver Cirrhosis1
4Unknown StatusTreatmentMechanical Ventilation Complication1
4Unknown StatusTreatmentSafety of Dexmedetomidine Sedation1
4Unknown StatusTreatmentTraumatic Brain Injury (TBI)1
4Unknown StatusTreatmentAdjunct to general anesthesia therapy1
4WithdrawnPreventionC.Surgical Procedure; Cardiac / Delirium1
4WithdrawnSupportive CareAlcohol Dependence / Respiration, Artificial1
4WithdrawnTreatmentPostoperative pain1
4WithdrawnTreatmentSleep1
Not AvailableActive Not RecruitingNot AvailableAAT Deficiency / AATD / Alpha-1 Antitrypsin Deficiency / Fibrosis, Liver1
Not AvailableActive Not RecruitingNot AvailableAortic Valve Stenosis1
Not AvailableActive Not RecruitingNot AvailableDexmedetomidine / Endoscopy, Gastrointestinal / Sedation therapy1
Not AvailableActive Not RecruitingNot AvailablePostoperative Cognitive Dysfunction1
Not AvailableActive Not RecruitingBasic ScienceAmnesia / Anaesthesia therapy / Anesthetics / Pain NOS / Sedation, Conscious1
Not AvailableActive Not RecruitingTreatmentIntubated Requiring Sedation for Greater Than 48 Hours1
Not AvailableActive Not RecruitingTreatmentPulmonary Diseases1
Not AvailableCompletedNot AvailableAnaesthesia therapy1
Not AvailableCompletedNot AvailableClinical Indications for Transesophageal Echocardiography1
Not AvailableCompletedNot AvailableEarly Gastric Cancer / Gastric Adenoma1
Not AvailableCompletedNot AvailableFeeling Anxious / Satisfaction / Sedation therapy / Tolerance1
Not AvailableCompletedNot AvailableMidazolam1
Not AvailableCompletedNot AvailablePain NOS1
Not AvailableCompletedNot AvailablePharmacokinetics / Voriconazole1
Not AvailableCompletedNot AvailablePsychomotor Agitation1
Not AvailableCompletedNot AvailableRhytidoplasty1
Not AvailableCompletedBasic ScienceCritical Care / Deep Sedation / Sedation, Conscious1
Not AvailableCompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers1
Not AvailableCompletedBasic ScienceHealthy Volunteers1
Not AvailableCompletedBasic SciencePharmacokinetics1
Not AvailableCompletedBasic ScienceSaccadic Eye Movements1
Not AvailableCompletedDiagnosticConscious Sedation Failure During Procedure1
Not AvailableCompletedDiagnosticEGD Procedure1
Not AvailableCompletedDiagnosticPain NOS1
Not AvailableCompletedDiagnosticSacroiliac Joint Pain / Sympathetically Maintained Pain1
Not AvailableCompletedOtherEndobronchial Ultrasound Guided Transbronchial Needle Aspiration1
Not AvailableCompletedPreventionAkathisia1
Not AvailableCompletedPreventionAnesthesia Morbidity / Children / Delirium on Emergence1
Not AvailableCompletedPreventionGeneral Surgery1
Not AvailableCompletedPreventionGeneral Surgery / Prostate Cancer1
Not AvailableCompletedPreventionPediatric Emergence Agitation and Pain1
Not AvailableCompletedPreventionPeripheral Obliterative Arteriopathy1
Not AvailableCompletedPreventionPost-Operative Nausea and Vomiting (PONV)1
Not AvailableCompletedPreventionPsychomotor Agitation1
Not AvailableCompletedPreventionTonsillitis1
Not AvailableCompletedSupportive CareAnaesthesia therapy / Body Temperature Changes1
Not AvailableCompletedSupportive CareFeeling Anxious1
Not AvailableCompletedSupportive CareFeeling Anxious / Pain NOS1
Not AvailableCompletedSupportive CareLiver Cirrhosis1
Not AvailableCompletedSupportive CareMalignancies1
Not AvailableCompletedSupportive CarePre Operative Anxiety1
Not AvailableCompletedSupportive CareTransient Hypertension1
Not AvailableCompletedTreatmentAnaesthesia therapy1
Not AvailableCompletedTreatmentAnxiety Preoperative / Midazolam Premedication / Premedication1
Not AvailableCompletedTreatmentBasal Cell Carcinoma (BCC) / Feeling Anxious / Skin Cancers / Squamous Cell Carcinoma (SCC)1
Not AvailableCompletedTreatmentCataracts1
Not AvailableCompletedTreatmentChronic Lung Diseases1
Not AvailableCompletedTreatmentCritical Illness1
Not AvailableCompletedTreatmentEchocardiography, Transesophageal1
Not AvailableCompletedTreatmentEndoscopy / Sedation therapy1
Not AvailableCompletedTreatmentFeeling Anxious1
Not AvailableCompletedTreatmentFeeling Anxious / Pain, Acute1
Not AvailableCompletedTreatmentFractures, Compression1
Not AvailableCompletedTreatmentHemodynamics After Spinal Anesthesia1
Not AvailableCompletedTreatmentIntubations1
Not AvailableCompletedTreatmentOther Surgical Procedures1
Not AvailableCompletedTreatmentPostoperative Cognitive Functions1
Not AvailableCompletedTreatmentPostoperative Pain Control / Wrist Injury1
Not AvailableCompletedTreatmentPsychomotor Agitation1
Not AvailableCompletedTreatmentRespiration Disorders1
Not AvailableCompletedTreatmentSedation in Critically Ill COPD Patients1
Not AvailableCompletedTreatmentSedation, Bronchoscopy1
Not AvailableCompletedTreatmentSepsis / Shock1
Not AvailableCompletedTreatmentSepsis / Traumas1
Not AvailableCompletedTreatmentStress, Psychological1
Not AvailableEnrolling by InvitationOtherIntestinal Microbiota / Ventilations, Mechanical1
Not AvailableEnrolling by InvitationTreatmentVirtual Reality1
Not AvailableNot Yet RecruitingNot AvailableDrug Drug Interaction (DDI) / Pharmacodynamics1
Not AvailableNot Yet RecruitingNot AvailablePostoperative pain1
Not AvailableNot Yet RecruitingBasic ScienceSedation therapy1
Not AvailableNot Yet RecruitingDevice FeasibilitySedation therapy / Spinal Anaesthesia1
Not AvailableNot Yet RecruitingOtherAnaesthesia therapy / Postoperative pain1
Not AvailableNot Yet RecruitingTreatmentAtherosclerosis / Coronary Artery Disease / Feeling Anxious / Pain, Acute / Vasospasm;Peripheral / Virtual Reality1
Not AvailableNot Yet RecruitingTreatmentBrachial Plexus Block / Shoulder Dislocation1
Not AvailableNot Yet RecruitingTreatmentGastro-esophageal Reflux Disease With Ulceration1
Not AvailableNot Yet RecruitingTreatmentHypercatabolism / Sedative, Hypnotic, or Anxiolytic Use Disorders1
Not AvailableNot Yet RecruitingTreatmentIntra-nasal Delevery Device / Procedural Sedation1
Not AvailableNot Yet RecruitingTreatmentObesity, Morbid1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Pressure (Hypertension) / High Cholesterol / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraine / Muscle Spasms / Nausea / Opioid Addiction / Pain NOS / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombotic events / Toxic effect of hydrocyanic acid and cyanides / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableRecruitingNot AvailableAnaesthesia therapy1
Not AvailableRecruitingNot AvailableBradycardia Sinus / Hydroxyzine / Reflex, Oculocardiac / Strabismus1
Not AvailableRecruitingNot AvailableCerebral Ischemia-Hypoxia1
Not AvailableRecruitingNot AvailableDepression1
Not AvailableRecruitingNot AvailableDrug Effect1
Not AvailableRecruitingNot AvailableGliomas1
Not AvailableRecruitingDiagnosticVentricular Tachycardia (VT)1
Not AvailableRecruitingHealth Services ResearchSedation therapy1
Not AvailableRecruitingOtherBronchoscopy1
Not AvailableRecruitingOtherSedation therapy / Spinal Anaesthesia1
Not AvailableRecruitingPreventionAnxiety, Preoperative / Child, Only: 4-6years / Children / Feeling Anxious / General Surgery / Surgical Procedure, Otorhinolaryngeal Surgery1
Not AvailableRecruitingPreventionIntubation; Difficult or Failed1
Not AvailableRecruitingPreventionPost-Operative Nausea and Vomiting (PONV)1
Not AvailableRecruitingTreatmentAcute Respiratory Failure1
Not AvailableRecruitingTreatmentAnoxic Encephalopathy / Cardiac Arrest / Refractory seizure disorders1
Not AvailableRecruitingTreatmentBronchoscopy / Sedation therapy1
Not AvailableRecruitingTreatmentChildren Under General Anaesthesia1
Not AvailableRecruitingTreatmentColonoscopy1
Not AvailableRecruitingTreatmentExtrusion of Tooth1
Not AvailableRecruitingTreatmentMajor Depressive Disorder (MDD)1
Not AvailableRecruitingTreatmentMajor Depressive Disorder (MDD) / Severe Depression / Treatment Resistant Depression (TRD)1
Not AvailableRecruitingTreatmentTonsillectomy1
Not AvailableSuspendedTreatmentPaediatric Flexible Bronchoscopy1
Not AvailableTerminatedNot AvailableVesicoureteral Reflux1
Not AvailableTerminatedOtherChronic Alcoholism1
Not AvailableTerminatedTreatmentBMI >30 kg/m2 / Sleep Apnea, Obstructive1
Not AvailableTerminatedTreatmentBipolar Disorder (BD)1
Not AvailableTerminatedTreatmentRespiratory Failure1
Not AvailableUnknown StatusNot AvailableFunctional disorders of the biliary tract / Pancreatic Diseases1
Not AvailableUnknown StatusBasic SciencePhobic Disorders1
Not AvailableUnknown StatusPreventionCystoscopy1
Not AvailableUnknown StatusScreeningAnesthesia Recovery Period / Delirium, Dementia, Cognitive Disorders / Mental Competency / Neurobehavioural Manifestation1
Not AvailableUnknown StatusSupportive CareDiverticulosis, Colonic / Malignant Neoplasm of Colon / Rectal Carcinoma1
Not AvailableUnknown StatusSupportive CarePacemaker Implantation / Pain NOS1
Not AvailableUnknown StatusSupportive CareSleeplessness1
Not AvailableUnknown StatusTreatmentAcute Agitation1
Not AvailableUnknown StatusTreatmentAnaesthesia therapy1
Not AvailableUnknown StatusTreatmentBronchoscopy; / Central Airway Stenosis / Interventional; / Noninvasive Positive Pressure Ventilation / Sedation therapy1
Not AvailableUnknown StatusTreatmentLiver Diseases1
Not AvailableWithdrawnNot AvailableTraumas1

Pharmacoeconomics

Manufacturers
  • Apothecon inc div bristol myers squibb
  • App pharmaceuticals llc
  • Astrazeneca pharmaceuticals lp
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Ben venue laboratories inc
  • Claris lifesciences ltd
  • Hospira inc
  • International medicated systems ltd
  • International medication systems ltd
  • Taylor pharmaceuticals
  • Wockhardt ltd
  • Hlr technology
  • Apotex inc richmond hill
  • Hi tech pharmacal co inc
  • Paddock laboratories inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Hoffmann la roche inc
Packagers
  • Akorn Inc.
  • APP Pharmaceuticals
  • A-S Medication Solutions LLC
  • B&B Pharmaceuticals
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Cardinal Health
  • Cura Pharmaceutical Co. Inc.
  • Dispensing Solutions
  • Ebewe Pharma
  • Hi Tech Pharmacal Co. Inc.
  • Hospira Inc.
  • Mikart Inc.
  • Novex Pharma
  • Paddock Labs
  • Patheon Inc.
  • Pharmedium
  • Physicians Total Care Inc.
  • Ranbaxy Laboratories
  • Roxane Labs
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
LiquidIntramuscular; Intravenous1 mg
LiquidIntramuscular; Intravenous5 mg
SolutionBuccal10 mg
SolutionBuccal2.5 mg
SolutionBuccal5 mg
SolutionBuccal7.5 mg
Injection, solutionIntramuscular; Intravenous10 mg/2mL
Injection, solutionIntramuscular; Intravenous2 mg/2mL
Injection, solutionIntravenous0.5 mg/1mL
Injection, solutionIntravenous1 mg/1mL
InjectionIntramuscular; Intravenous1 mg/1mL
InjectionIntramuscular; Intravenous10 mg/2mL
InjectionIntramuscular; Intravenous2 mg/2mL
InjectionIntramuscular; Intravenous5 mg/1mL
Injection, solutionIntramuscular; Intravenous1 mg/1mL
Injection, solutionIntramuscular; Intravenous5 mg/1mL
SyrupOral10 mg/5mL
SyrupOral2 mg/1mL
SolutionIntramuscular; Intravenous1 mg
SolutionIntramuscular; Intravenous5 mg
TrocheSublingual
Injection, solutionIntramuscular5 mg/1mL
Prices
Unit descriptionCostUnit
Midazolam 5 mg/ml3.9USD ml
Midazolam-nacl 2 mg/ml inj2.31USD ml
Midazolam hcl 5 mg/ml vial1.18USD ml
Midazolam-nacl 1 mg/ml inj1.13USD ml
Midazolam hcl 2 mg/ml syrup1.08USD ml
Midazolam 1 mg/ml isecure syr0.73USD ml
Midazolam hcl 1 mg/ml vial0.26USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)161-164MSDS
boiling point (°C)497MSDS
water solubilitysolubleFDA label
Predicted Properties
PropertyValueSource
Water Solubility0.00987 mg/mLALOGPS
logP3.89ALOGPS
logP3.33ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)6.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area30.18 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity99.43 m3·mol-1ChemAxon
Polarizability32.7 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9724
Caco-2 permeable+0.8866
P-glycoprotein substrateNon-substrate0.5074
P-glycoprotein inhibitor IInhibitor0.5587
P-glycoprotein inhibitor IIInhibitor0.8388
Renal organic cation transporterInhibitor0.7476
CYP450 2C9 substrateNon-substrate0.7366
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7194
CYP450 1A2 substrateInhibitor0.8586
CYP450 2C9 inhibitorInhibitor0.7132
CYP450 2D6 inhibitorNon-inhibitor0.6887
CYP450 2C19 inhibitorInhibitor0.6554
CYP450 3A4 inhibitorNon-inhibitor0.5214
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9001
Ames testNon AMES toxic0.8024
CarcinogenicityNon-carcinogens0.7703
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.1488 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9827
hERG inhibition (predictor II)Non-inhibitor0.7379
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-03di-3839000000-42781254e15bcd5b31b6
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-2411220f611ba30ef225
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0009000000-c724b297ae99edb399d3
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004l-0098000000-b57c162c4eeaad9ef111
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0090000000-a3133528f5491f4c9a6b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05fs-0290000000-ee126555f849ecfff795
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0009000000-4ae622c7b53369b0cfb1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0019000000-00c3c9e2813a454acda1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-002f-0093000000-a8ca99ef6c84536bff07
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0091000000-3edc4aa6f67d99b789a8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0abd-0290000000-aa5e16437618ad2adb86
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05fs-0490000000-a323090224c5b01e3990
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0189000000-6e704a4a2a65211394ab
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03di-0910000000-98021a5812f1663e9397

Taxonomy

Description
This compound belongs to the class of organic compounds known as imidazo[1,5-a][1,4]benzodiazepines. These 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
Fluorobenzenes / 1,4-diazepines / N-substituted imidazoles / Aryl fluorides / Aryl chlorides / Heteroaromatic compounds / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds
show 3 more
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
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
diazepine (CHEBI:6931)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...
Gene Name
GABRA1
Uniprot ID
P14867
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-1
Molecular Weight
51801.395 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Haefely W: Benzodiazepine interactions with GABA receptors. Neurosci Lett. 1984 Jun 29;47(3):201-6. [PubMed:6147796]
  4. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA2
Uniprot ID
P47869
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-2
Molecular Weight
51325.85 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Transporter activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA5
Uniprot ID
P31644
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-5
Molecular Weight
52145.645 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA3
Uniprot ID
P34903
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-3
Molecular Weight
55164.055 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA4
Uniprot ID
P48169
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-4
Molecular Weight
61622.645 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Potentiator
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name
GABRA6
Uniprot ID
Q16445
Uniprot Name
Gamma-aminobutyric acid receptor subunit alpha-6
Molecular Weight
51023.69 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [PubMed:11752090]
  2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [PubMed:18384456]
  3. Tan KR, Rudolph U, Luscher C: Hooked on benzodiazepines: GABAA receptor subtypes and addiction. Trends Neurosci. 2011 Apr;34(4):188-97. doi: 10.1016/j.tins.2011.01.004. Epub 2011 Feb 25. [PubMed:21353710]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Foti RS, Rock DA, Wienkers LC, Wahlstrom JL: Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos. 2010 Jun;38(6):981-7. doi: 10.1124/dmd.110.032094. Epub 2010 Mar 4. [PubMed:20203109]
  2. Pelkonen O, Maenpaa J, Taavitsainen P, Rautio A, Raunio H: Inhibition and induction of human cytochrome P450 (CYP) enzymes. Xenobiotica. 1998 Dec;28(12):1203-53. [PubMed:9890159]
  3. Zhou S, Chan E, Lim LY, Boelsterli UA, Li SC, Wang J, Zhang Q, Huang M, Xu A: Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr Drug Metab. 2004 Oct;5(5):415-42. [PubMed:15544435]
  4. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, Hamman MA, Hall SD, Wrighton SA: Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002 Aug;30(8):883-91. [PubMed:12124305]
  5. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. [PubMed:12433827]
  6. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. [PubMed:12065442]
  7. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Patki KC, Von Moltke LL, Greenblatt DJ: In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos. 2003 Jul;31(7):938-44. [PubMed:12814972]
  2. Wandel C, Bocker R, Bohrer H, Browne A, Rugheimer E, Martin E: Midazolam is metabolized by at least three different cytochrome P450 enzymes. Br J Anaesth. 1994 Nov;73(5):658-61. [PubMed:7826796]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Klieber S, Hugla S, Ngo R, Arabeyre-Fabre C, Meunier V, Sadoun F, Fedeli O, Rival M, Bourrie M, Guillou F, Maurel P, Fabre G: Contribution of the N-glucuronidation pathway to the overall in vitro metabolic clearance of midazolam in humans. Drug Metab Dispos. 2008 May;36(5):851-62. doi: 10.1124/dmd.107.019539. Epub 2008 Feb 6. [PubMed:18256203]
  2. Hyland R, Osborne T, Payne A, Kempshall S, Logan YR, Ezzeddine K, Jones B: In vitro and in vivo glucuronidation of midazolam in humans. Br J Clin Pharmacol. 2009 Apr;67(4):445-54. doi: 10.1111/j.1365-2125.2009.03386.x. [PubMed:19371318]
  3. Seo KA, Bae SK, Choi YK, Choi CS, Liu KH, Shin JG: Metabolism of 1'- and 4-hydroxymidazolam by glucuronide conjugation is largely mediated by UDP-glucuronosyltransferases 1A4, 2B4, and 2B7. Drug Metab Dispos. 2010 Nov;38(11):2007-13. doi: 10.1124/dmd.110.035295. Epub 2010 Aug 16. [PubMed:20713656]
  4. Liu Y, She M, Wu Z, Dai R: The inhibition study of human UDP-glucuronosyltransferases with cytochrome P450 selective substrates and inhibitors. J Enzyme Inhib Med Chem. 2011 Jun;26(3):386-93. doi: 10.3109/14756366.2010.518965. Epub 2010 Oct 13. [PubMed:20939765]

Drug created on June 13, 2005 07:24 / Updated on February 18, 2019 20:23