Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:27:24 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2859
Identification
Common NameMidazolam
ClassSmall Molecule
DescriptionA 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.
Compound Type
  • Adjuvant, Anesthesia
  • Anesthetic, Intravenous
  • Anti-Anxiety Agent
  • Drug
  • GABA Modulator
  • Hypnotic and Sedative
  • Metabolite
  • Organic Compound
  • Organochloride
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Anquil
Benzosed
Buccolam
Dalam
Damizol
Dea No. 2884
Demizolam
Doricum
Dormicum
Dormid
Dormipron
Dormire
Dormitol
Dormixal
Dormonid
Drimnorth
Epistatus
Flormidal
Fulsed
Fulsed Injection
Garen
Gobbizolam
Hipnazolam
Hipnoz
Hypnofast
Hypnovel
Ipnovel
Midazolam Base
Midazolamum
Nocturna
Setam
Talentum
Terap
Versed
Chemical FormulaC18H13ClFN3
Average Molecular Mass325.767 g/mol
Monoisotopic Mass325.078 g/mol
CAS Registry Number59467-70-8
IUPAC Name12-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 Namemidazolam
SMILESCC1=NC=C2CN=C(C3=CC=CC=C3F)C3=C(C=CC(Cl)=C3)N12
InChI IdentifierInChI=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 KeyInChIKey=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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzodiazepines
Sub Class1,4-benzodiazepines
Direct ParentImidazo[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 FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point159°C
Boiling PointNot Available
Solubility0.024 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0099 g/LALOGPS
logP3.89ALOGPS
logP3.33ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)6.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area30.18 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity99.43 m³·mol⁻¹ChemAxon
Polarizability32.7 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-002g-5092000000-4478c9440e5f31cecc49View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-03di-0910000000-98021a5812f1663e9397View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0009000000-2411220f611ba30ef225View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0009000000-c724b297ae99edb399d3View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004l-0098000000-b57c162c4eeaad9ef111View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0006-0090000000-a3133528f5491f4c9a6bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05fs-0290000000-ee126555f849ecfff795View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0009000000-4ae622c7b53369b0cfb1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0019000000-00c3c9e2813a454acda1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-002f-0093000000-a8ca99ef6c84536bff07View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-0091000000-3edc4aa6f67d99b789a8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0abd-0290000000-aa5e16437618ad2adb86View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-05fs-0490000000-a323090224c5b01e3990View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0189000000-6e704a4a2a65211394abView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0910000000-98021a5812f1663e9397View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0019000000-75a4c3ae620bf5e6503aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0029000000-6729271ff5dbb7d43009View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a7i-1390000000-39f40fc60488c1207b28View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0009000000-b77187b6c2f47259d8d6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0029000000-91cf028d658129087ce6View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ufu-5091000000-645cab1e9777fb49b7b2View in MoNA
MSMass Spectrum (Electron Ionization)splash10-03di-3839000000-42781254e15bcd5b31b6View in MoNA
Toxicity Profile
Route of ExposureRapidly 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 ToxicityIt 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.
MetabolismMidazolam 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 ValuesLD50: 825 mg/kg (Oral, Rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIntravenous 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 LevelNot Available
Health EffectsThey cause slurred speech, disorientation and "drunken" behavior. They are physically and psychologically addictive.
SymptomsNot Available
TreatmentTreatment 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. (8)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00683
HMDB IDHMDB14821
PubChem Compound ID4192
ChEMBL IDCHEMBL655
ChemSpider ID4047
KEGG IDC07524
UniProt IDNot Available
OMIM ID
ChEBI ID127611
BioCyc IDNot Available
CTD IDNot Available
Stitch IDMidazolam
PDB ID08J
ACToR IDNot Available
Wikipedia LinkMidazolam
References
Synthesis Reference

Madhup K. Dhaon, “Process for the preparation of midazolam.” U.S. Patent US6262260, issued August, 1979.

MSDSLink
General References
  1. 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. [17287588 ]
  2. Skerritt JH, Johnston GA: Enhancement of GABA binding by benzodiazepines and related anxiolytics. Eur J Pharmacol. 1983 May 6;89(3-4):193-8. [6135616 ]
  3. 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. [10030438 ]
  4. 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. [2894998 ]
  5. Vermeeren A: Residual effects of hypnotics: epidemiology and clinical implications. CNS Drugs. 2004;18(5):297-328. [15089115 ]
  6. FDA label
  7. Drugs.com [Link]
  8. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

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
Molecular Weight:
51325.85 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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
Molecular Weight:
55164.055 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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
Molecular Weight:
52145.645 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRB1
Uniprot ID:
P18505
Molecular Weight:
54234.085 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB2
Uniprot ID:
P47870
Molecular Weight:
59149.895 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-gated chloride 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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRB3
Uniprot ID:
P28472
Molecular Weight:
54115.04 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-a receptor 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:
GABRD
Uniprot ID:
O14764
Molecular Weight:
50707.835 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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:
GABRE
Uniprot ID:
P78334
Molecular Weight:
57971.175 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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:
GABRG1
Uniprot ID:
Q8N1C3
Molecular Weight:
53594.49 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
Gene Name:
GABRG2
Uniprot ID:
P18507
Molecular Weight:
54161.78 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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:
GABRG3
Uniprot ID:
Q99928
Molecular Weight:
54288.16 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-a receptor 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. In the uterus, the function of the receptor appears to be related to tissue contractility. The binding of this pI subunit with other GABA(A) receptor subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone.
Gene Name:
GABRP
Uniprot ID:
O00591
Molecular Weight:
50639.735 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-a receptor 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. Rho-1 GABA receptor could play a role in retinal neurotransmission.
Gene Name:
GABRR1
Uniprot ID:
P24046
Molecular Weight:
55882.91 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-a receptor 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. Rho-2 GABA receptor could play a role in retinal neurotransmission.
Gene Name:
GABRR2
Uniprot ID:
P28476
Molecular Weight:
54150.41 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
General Function:
Gaba-a receptor 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:
GABRR3
Uniprot ID:
A8MPY1
Molecular Weight:
54271.1 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
  3. Iorio LC, Barnett A, Billard W: Selective affinity of 1-N-trifluoroethyl benzodiazepines for cerebellar type 1 receptor sites. Life Sci. 1984 Jul 2;35(1):105-13. [6738302 ]
  4. Wamsley JK, Golden JS, Yamamura HI, Barnett A: Autoradiographic demonstration of the selectivity of two 1-N-trifluoroethyl benzodiazepines for the BZD-1 receptors in the rat brain. Pharmacol Biochem Behav. 1985 Dec;23(6):973-8. [2867566 ]
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC508.1 uMNot AvailableBindingDB 21363
IC50>33 uMNot AvailableBindingDB 21363
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
  2. Bass JY, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Mills WY, Navas F 3rd, Parks DJ, Smalley TL Jr, Spearing PK, Todd D, Williams SP, Wisely GB: Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene. Bioorg Med Chem Lett. 2011 Feb 15;21(4):1206-13. doi: 10.1016/j.bmcl.2010.12.089. Epub 2010 Dec 23. [21256005 ]
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
Molecular Weight:
61622.645 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
Molecular Weight:
51023.69 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Transmembrane signaling receptor 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:
GABRQ
Uniprot ID:
Q9UN88
Molecular Weight:
72020.875 Da
References
  1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [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. [18384456 ]
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 21363
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
23. GABA-A receptor (anion channel) (Protein Group)
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. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Included Proteins:
P14867 , P47869 , P34903 , P48169 , P31644 , Q16445 , P18505 , P47870 , P28472 , O14764 , P78334 , Q8N1C3 , P18507 , Q99928 , O00591 , Q9UN88