Identification

Name
Lorazepam
Accession Number
DB00186  (APRD00116)
Type
Small Molecule
Groups
Approved
Description

A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.

Structure
Thumb
Synonyms
  • Loracepam
  • Lorazepam
  • o-Chlorooxazepam
  • o-Chloroxazepam
External IDs
WY-4036
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AtivanTablet1 mgSublingualPfizer1994-12-31Not applicableCanada
AtivanInjection, solution4 mg/1mLIntramuscular; IntravenousBaxter Laboratories2009-09-242014-01-31Us
AtivanTablet1 mg/1OralPhysicians Total Care, Inc.2010-03-162012-06-30Us
AtivanInjection4.0 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.1980-07-25Not applicableUs
AtivanTablet1 mg/1OralMckesson Rxpak Inc2013-05-01Not applicableUs
AtivanTablet1 mg/1OralStat Rx USA2010-03-16Not applicableUs
AtivanTablet2 mgOralPfizer1994-12-31Not applicableCanada
AtivanTablet1 mg/1OralValeant Pharmaceuticals North America LLC2013-05-01Not applicableUs
AtivanInjection2.0 mg/1mLIntramuscular; IntravenousWest-Ward Pharmaceuticals Corp.1980-07-25Not applicableUs
AtivanTablet1 mg/1OralBTA Pharmaceuticals Inc.2010-03-162015-01-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-lorazepam Tab 0.5mgTablet0.5 mgOralApotex Corporation1985-12-31Not applicableCanada
Apo-lorazepam Tab 1mgTablet1 mgOralApotex Corporation1985-12-31Not applicableCanada
Apo-lorazepam Tab 2mgTablet2 mgOralApotex Corporation1985-12-31Not applicableCanada
Dom-lorazepamTablet.5 mgOralDominion Pharmacal2002-04-25Not applicableCanada
Dom-lorazepamTablet2 mgOralDominion Pharmacal2002-04-25Not applicableCanada
Dom-lorazepamTablet1 mgOralDominion Pharmacal2002-04-25Not applicableCanada
LorazepamTablet2 mg/1OralRemedy Repack2016-10-10Not applicableUs
LorazepamTablet2 mg/1OralGoldline Laboratories, Inc.2010-01-212010-11-30Us
LorazepamTablet2 mg/1OralRemedy Repack2013-05-082013-05-09Us
LorazepamTablet2 mg/1OralRebel Distributors1988-04-15Not applicableUs
International/Other Brands
Almazine (Psyco Remedies) / Anxiedin (U-Liang) / Idalprem (Novartis) / Lorabenz / Lorsilan (Belupo) / Somagerol / Temesta (Wyeth) / Wypax (Wyeth KK)
Categories
UNII
O26FZP769L
CAS number
846-49-1
Weight
Average: 321.158
Monoisotopic: 320.011932988
Chemical Formula
C15H10Cl2N2O2
InChI Key
DIWRORZWFLOCLC-UHFFFAOYSA-N
InChI
InChI=1S/C15H10Cl2N2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)
IUPAC Name
7-chloro-5-(2-chlorophenyl)-3-hydroxy-2,3-dihydro-1H-1,4-benzodiazepin-2-one
SMILES
OC1N=C(C2=CC=CC=C2Cl)C2=C(NC1=O)C=CC(Cl)=C2

Pharmacology

Indication

For the management of anxiety disorders, and for treatment of status epilepticus.

Associated Conditions
Associated Therapies
Pharmacodynamics

Lorazepam, a benzodiazepine not transformed to active metabolites, is used to treat anxiety, status epilepticus, and for sedation induction and anterograde amnesia.

Mechanism of action

Lorazepam binds to an allosteric site on GABA-A receptors, which are pentameric ionotropic receptors in the CNS. Binding potentiates the effects of the inhibitory neurotransmitter GABA, which upon binding opens the chloride channel in the receptor, allowing chloride influx and causing hyperpolerization of the neuron.

TargetActionsOrganism
AGABA-A receptor (anion channel)
positive allosteric modulator
Human
UTranslocator protein
other
Human
Absorption

Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered, lorazepam is completely and rapidly absorbed. It achieves max serum concentration in 3 hours. The max serum concentration of a 4 mg dose is 48 ng/mL.

Volume of distribution

1.3 L/kg. Unbound lorazepam can cross the blood-brain-barrier via passive diffusion.

Protein binding

91±2% bound to plasma proteins when given parenterally. When given orally, it is 85% bound to plasma proteins.

Metabolism

Lorazepam is hepatically metabolized and is extensively conjugated to the 3-0-phenolic glucuronide. This is an inactive metabolite and is eliminated mainly by the kidneys.

Route of elimination

When a single 2 mg oral dose is give to healthy subjects, 88±4% of the administered dose was recovered in urine and 7±2% was recovered in feces. The percent of administered dose recovered in urine as lorazepam glucuronide was 74±4%. Only 0.3% of the dose was recovered as unchanged lorazepam, and the remainder of the radioactivity represented minor metabolites.

Half life

Parenteral administration = 14±5 hours; Oral administration = 2 hours.

Clearance

Total clearance, parenteral administration = 1.1±0.4 mL/min/kg.

Toxicity

The most important clinical adverse event caused by lorazepam is respiratory depression. LD50, mouse, oral = 1850 mg/kg.

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lorazepam.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lorazepam.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Lorazepam is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Lorazepam 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 Lorazepam is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lorazepam.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lorazepam.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Lorazepam is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Lorazepam.
Food Interactions
  • Avoid alcohol.
  • Avoid excessive quantities of coffee or tea (Caffeine).
  • Take with food.

References

Synthesis Reference

Igor Lifshitz, "Process for preparing pure crystalline lorazepam." U.S. Patent US20010039340, issued November 08, 2001.

US20010039340
General References
  1. Kemper N, Poser W, Poser S: [Benzodiazepine dependence: addiction potential of the benzodiazepines is greater than previously assumed (author's transl)]. Dtsch Med Wochenschr. 1980 Dec 5;105(49):1707-12. [PubMed:7439058]
  2. Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6. [PubMed:6144459]
  3. Maltais F, Laberge F, Laviolette M: A randomized, double-blind, placebo-controlled study of lorazepam as premedication for bronchoscopy. Chest. 1996 May;109(5):1195-8. [PubMed:8625666]
  4. Heisterkamp DV, Cohen PJ: The effect of intravenous premedication with lorazepam (ativan), pentobarbitone or diazepam on recall. Br J Anaesth. 1975 Jan;47(1):79-81. [PubMed:238548]
  5. Milligan DW, Howard MR, Judd A: Premedication with lorazepam before bone marrow biopsy. J Clin Pathol. 1987 Jun;40(6):696-8. [PubMed:3611398]
External Links
Human Metabolome Database
HMDB0014332
KEGG Drug
D00365
PubChem Compound
3958
PubChem Substance
46508468
ChemSpider
3821
BindingDB
50292627
ChEBI
6539
ChEMBL
CHEMBL580
Therapeutic Targets Database
DAP000237
PharmGKB
PA450267
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lorazepam
ATC Codes
N05BA06 — LorazepamN05BA56 — Lorazepam, combinations
AHFS Codes
  • 28:24.08 — Benzodiazepines
FDA label
Download (540 KB)
MSDS
Download (81.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableRecreational CNS Depressant Use1
1CompletedBasic ScienceAlzheimer's Disease (AD)1
1CompletedBasic ScienceEpilepsies1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedDiagnosticHealthy Volunteers1
1CompletedPreventionPost-Operative Delirium1
1CompletedSupportive CareCatatonia / Nodding Syndrome1
1CompletedTreatmentDementias1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1CompletedTreatmentVoice Disorders1
1CompletedTreatmentRefractory seizure disorders1
1TerminatedDiagnosticSchizophrenic Disorders1
1, 2WithdrawnTreatmentSodium Oxybate / Substance-Related Disorders1
2Active Not RecruitingSupportive CareAdvanced Cancers1
2CompletedBasic ScienceReflex Epilepsy, Photosensitive1
2CompletedPreventionDelirium1
2CompletedTreatmentAlcohol Dependence1
2CompletedTreatmentAlcohol Withdrawal Syndrome(AWS)1
2CompletedTreatmentAnxiety Disorders1
2CompletedTreatmentBipolar Disorder (BD) / Mania / Manic Disorder / Manic syndromes / Schizoaffective Disorders1
2CompletedTreatmentCocaine Dependence Related Impairments in Motivation for Change, and in Cue-induced Arousal / Dependence, Cocaine1
2CompletedTreatmentEpilepsies1
2CompletedTreatmentFeeling Anxious1
2Not Yet RecruitingTreatmentObsessive Compulsive Disorder (OCD)1
2TerminatedSupportive CareNausea / Unspecified Childhood Solid Tumor, Protocol Specific / Vomiting1
2, 3CompletedTreatmentCritical Illness1
2, 3CompletedTreatmentRefractory seizure disorders1
2, 3Not Yet RecruitingSupportive CareCaregivers / Delirium / Locally Advanced Malignant Neoplasm / Metastatic Malignant Neoplasm / Recurrent Malignant Neoplasm1
2, 3WithdrawnTreatmentSeizures1
3CompletedBasic ScienceHealthy Volunteers1
3CompletedTreatmentAcute Agitation / Schizoaffective Disorders / Schizophrenic Disorders1
3CompletedTreatmentConvulsions / Refractory seizure disorders1
3CompletedTreatmentEpilepsies / Refractory seizure disorders1
3CompletedTreatmentPerioperative Anxiety1
3CompletedTreatmentRefractory seizure disorders / Seizures1
3CompletedTreatmentSleep Initiation and Maintenance Disorders1
3CompletedTreatmentVertigo, Peripheral1
3CompletedTreatmentRefractory seizure disorders3
3TerminatedSupportive CareCancer, Breast / Lung Cancers / Pain NOS1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentConvulsions / Refractory seizure disorders1
3TerminatedTreatmentEpilepsia Partialis Continua / Epilepsies / Kojewnikov's Epilepsy1
3TerminatedTreatmentSleep Initiation and Maintenance Disorders1
3Unknown StatusBasic ScienceVolunteers Aged Between 65 and 75 Years Old1
4CompletedNot AvailableCognitive Deficits1
4CompletedDiagnosticAnxiety Disorders / Generalized Anxiety Disorder (GAD)1
4CompletedOtherHealthy Volunteers1
4CompletedTreatmentAcute Agitation1
4CompletedTreatmentAcute Alcohol Withdrawal Syndrome / Alcohol Withdrawal Syndrome(AWS)1
4CompletedTreatmentAlcohol Dependence1
4CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD) / Unipolar Depression1
4CompletedTreatmentFeeling Anxious1
4CompletedTreatmentGeneralized Anxiety Disorder (GAD)1
4CompletedTreatmentSedation therapy1
4RecruitingPreventionAlcohol Dependence / Alcohol Use Disorder (AUD) / Alcohol Withdrawal Syndrome(AWS) / Heavy Drinking / Traumas1
4RecruitingTreatmentAlcohol Withdrawal Syndrome(AWS)1
4RecruitingTreatmentAnticholinergics Toxicity1
4RecruitingTreatmentCardiac Arrest / Hypothermia1
4RecruitingTreatmentOral Sedation and Cervical Dilator Pain1
4RecruitingTreatmentSedation in Intensive Care Unit Patients1
4TerminatedTreatmentHaloperidol Causing Adverse Effects in Therapeutic Use / Lorazepam Causing Adverse Effects in Therapeutic Use / Loxapine Causing Adverse Effects in Therapeutic Use / Psychomotor Agitation1
4Unknown StatusSupportive CarePatient Satisfaction for Bronchoscopy1
Not AvailableActive Not RecruitingNot AvailableAAT Deficiency / AATD / Alpha-1 Antitrypsin Deficiency / Fibrosis, Liver1
Not AvailableCompletedNot AvailableHealthy Volunteers1
Not AvailableCompletedBasic ScienceAnxiety Disorders1
Not AvailableCompletedBasic ScienceCognition1
Not AvailableCompletedBasic ScienceHealthy Volunteers2
Not AvailableCompletedPreventionAlcohol Withdrawal Delirium1
Not AvailableCompletedScreeningAlzheimer's Disease (AD)1
Not AvailableCompletedSupportive CareFocus of Study: Absorption of the Three Components in the Topical ABH Gel in Healthy Volunteers, and Determine if There Are Any Adverse Effects / Healthy Volunteers1
Not AvailableCompletedSupportive CareInfertilities / Subfertility1
Not AvailableCompletedSupportive CareNausea / Vomiting1
Not AvailableCompletedTreatmentAlcohol Withdrawal Syndrome(AWS)1
Not AvailableCompletedTreatmentBenign Paroxysmal Positional Vertigo (BPPV)1
Not AvailableCompletedTreatmentContraception / Inhalation of Nitrous Oxide1
Not AvailableCompletedTreatmentHip Fracture Surgery / Post Operative Pain Control1
Not AvailableCompletedTreatmentOpiate Addiction1
Not AvailableRecruitingBasic SciencePain NOS1
Not AvailableRecruitingTreatmentAnoxic Encephalopathy / Cardiac Arrest / Refractory seizure disorders1
Not AvailableUnknown StatusDiagnosticHealthy Volunteers1
Not AvailableUnknown StatusPreventionPost Traumatic Stress Disorder (PTSD) / Sleep Deprivation1
Not AvailableUnknown StatusSupportive CareNon-Hodgkin's Lymphoma (NHL)1
Not AvailableWithdrawnPreventionPolymorphism, Genetic / Post-Operative Nausea and Vomiting (PONV)1

Pharmacoeconomics

Manufacturers
  • Amneal pharmaceuticals
  • Paddock laboratories inc
  • Pharmaceutical assoc inc
  • Roxane laboratories inc
  • Baxter healthcare corp anesthesia critical care
  • Akorn inc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Dava pharmaceuticals inc
  • Hospira inc
  • International medication systems ltd
  • Marsam pharmaceuticals llc
  • Taylor pharmaceuticals
  • Watson laboratories inc
  • Bedford laboratories
  • Biovail laboratories inc
  • Quantum pharmics ltd
  • Actavis elizabeth llc
  • American therapeutics inc
  • Excellium pharmaceutical inc
  • Halsey drug co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Superpharm corp
  • Usl pharma inc
  • Vintage pharmaceuticals inc
  • Warner chilcott div warner lambert co
Packagers
  • Actavis Group
  • Aidarex Pharmacuticals LLC
  • Akorn Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bryant Ranch Prepack
  • BTA Pharmaceuticals
  • Cardinal Health
  • Caremark LLC
  • Centaur Pharmaceuticals Pvt Ltd.
  • Cipla Ltd.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Direct Dispensing Inc.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Excellium Pharmaceutical Inc.
  • Goldline Laboratories Inc.
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Hospira Inc.
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Mckesson Corp.
  • Meda AB
  • Medisca Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mutual Pharmaceutical Co.
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • Paddock Labs
  • Palmetto Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedium
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Talbert Medical Management Corp.
  • Taylor Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Va Cmop Dallas
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous4.0 mg/1mL
TabletOral0.5 mg
TabletOral1 mg
TabletOral2 mg
TabletSublingual0.5 mg
TabletSublingual1 mg
TabletSublingual2 mg
LiquidIntramuscular; Intravenous4 mg
SolutionIntramuscular; Intravenous4 mg
ConcentrateOral2 mg/1mL
InjectionIntramuscular2 mg/1mL
InjectionIntramuscular; Intravenous2 mg/1mL
InjectionIntramuscular; Intravenous2.0 mg/1mL
InjectionIntramuscular; Intravenous4 mg/1mL
Injection, solutionIntramuscular; Intravenous2 mg/1mL
Injection, solutionIntramuscular; Intravenous4 mg/1mL
LiquidOral2 mg/1mL
Solution, concentrateOral2 mg/1mL
TabletOral.5 mg/1
TabletOral0.5 mg/1
TabletOral1 mg/1
TabletOral1.0 mg
TabletOral2 mg/1
TabletOral2.0 mg
SolutionIntramuscular; Intravenous2 mg
TabletOral.5 mg
Prices
Unit descriptionCostUnit
LORazepam Intensol 2 mg/ml Concentrate 30ml Bottle44.99USD bottle
Lorazepam powder20.81USD g
Lorazepam 4 mg/ml vial9.59USD ml
Lorazepam 2 mg/ml vial2.5USD ml
Ativan 2 mg tablet2.3USD tablet
Ativan 4 mg/ml vial2.16USD ml
Ativan 1 mg tablet1.96USD tablet
Lorazepam intensol 2 mg/ml1.6USD ml
Lorazepam-ns 60 mg/60 ml bag1.53USD ml
Ativan 0.5 mg tablet1.37USD tablet
Lorazepam-d5w 100 mg/100 ml1.16USD ml
Lorazepam-ns 100 mg/100 ml bag1.16USD ml
Lorazepam 2 mg tablet1.01USD tablet
Ativan 2 mg/ml vial0.9USD ml
Lorazepam 1 mg tablet0.69USD tablet
Lorazepam 0.5 mg tablet0.55USD tablet
Ativan 2 mg Sublingual Tablet0.24USD tablet
Ativan 1 mg Sublingual Tablet0.15USD tablet
Ativan 0.5 mg Sublingual Tablet0.12USD tablet
Apo-Lorazepam 2 mg Tablet0.07USD tablet
Novo-Lorazem 2 mg Tablet0.07USD tablet
Pms-Lorazepam 2 mg Tablet0.07USD tablet
Apo-Lorazepam 1 mg Tablet0.05USD tablet
Novo-Lorazem 1 mg Tablet0.05USD tablet
Pms-Lorazepam 1 mg Tablet0.05USD tablet
Apo-Lorazepam 0.5 mg Tablet0.04USD tablet
Novo-Lorazem 0.5 mg Tablet0.04USD tablet
Pms-Lorazepam 0.5 mg Tablet0.04USD tablet
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)192-194British Patent 1,022,642.
water solubility80 mg/LMERCK INDEX (1996)
logP2.39HANSCH,C ET AL. (1995)
logS-3.6ADME Research, USCD
pKa13MERCK INDEX (1996); pK1
Predicted Properties
PropertyValueSource
Water Solubility0.0176 mg/mLALOGPS
logP2.98ALOGPS
logP3.53ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)10.61ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area61.69 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity82.7 m3·mol-1ChemAxon
Polarizability30.33 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9826
Blood Brain Barrier+0.9641
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.517
P-glycoprotein inhibitor INon-inhibitor0.8866
P-glycoprotein inhibitor IINon-inhibitor0.9167
Renal organic cation transporterNon-inhibitor0.8812
CYP450 2C9 substrateNon-substrate0.7692
CYP450 2D6 substrateNon-substrate0.8685
CYP450 3A4 substrateSubstrate0.5631
CYP450 1A2 substrateInhibitor0.8262
CYP450 2C9 inhibitorNon-inhibitor0.5063
CYP450 2D6 inhibitorNon-inhibitor0.8445
CYP450 2C19 inhibitorInhibitor0.5065
CYP450 3A4 inhibitorNon-inhibitor0.6563
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6407
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.7711
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8229 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.999
hERG inhibition (predictor II)Non-inhibitor0.8734
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
GC-MS Spectrum - EI-BGC-MSsplash10-009i-6791000000-942b7493f1e9fc3d12be
Mass Spectrum (Electron Ionization)MSsplash10-002r-4981000000-a567f7beb26ee18d061c
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-QFT , negativeLC-MS/MSsplash10-001i-0091000000-04730f82e569df7febdd
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0390000000-dd63d93f2fa81cbb5928
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0930000000-3ecf1f2f10049a3cfee2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0910000000-95d23a9a121bf45ef8bf
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-cdbe26e697f259770c28
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-4046d54b4dd9bf7968be
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-001i-0091000000-abaf38ed3aa6e7d51245
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052b-9000000000-dda683413448d0461123
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0009000000-53bbea620bd1e8b49eb3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fb9-0095000000-793565a97e3afc2ce858
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0090000000-41097b8a64363c5e2f94
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0290000000-a0694111a3943eca2b53
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-004i-0690000000-5a4728cb7e2473fc6b3c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01rf-0940000000-39d041fbab4fb67a5c41
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00b9-0298000000-986499cda13643ef7d85
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00b9-0196000000-2e53b39b27c66ec73fd2

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,4-benzodiazepines. These are organic compounds containing a benzene ring fused to a 1,4-azepine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzodiazepines
Sub Class
1,4-benzodiazepines
Direct Parent
1,4-benzodiazepines
Alternative Parents
Alpha amino acids and derivatives / Chlorobenzenes / Aryl chlorides / Secondary carboxylic acid amides / Lactams / Ketimines / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Alkanolamines / Organopnictogen compounds
show 4 more
Substituents
1,4-benzodiazepine / Alpha-amino acid or derivatives / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Carboxamide group / Ketimine
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein group
Organism
Human
Pharmacological action
Yes
Actions
Positive allosteric modulator
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...

Components:
References
  1. 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]
  2. ChEMBL Compound Report Card [Link]
Details
2. Translocator protein
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other
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 l...
Gene Name
TSPO
Uniprot ID
P30536
Uniprot Name
Translocator protein
Molecular Weight
18827.81 Da
References
  1. Venneti S, Lopresti BJ, Wiley CA: The peripheral benzodiazepine receptor (Translocator protein 18kDa) in microglia: from pathology to imaging. Prog Neurobiol. 2006 Dec;80(6):308-22. Epub 2006 Dec 6. [PubMed:17156911]
  2. Park CH, Carboni E, Wood PL, Gee KW: Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line. Glia. 1996 Jan;16(1):65-70. [PubMed:8787774]
  3. Uusi-Oukari M, Korpi ER: Specific alterations in the cerebellar GABA(A) receptors of an alcohol-sensitive ANT rat line. Alcohol Clin Exp Res. 1991 Mar;15(2):241-8. [PubMed:1647706]
  4. Miller EI, Wylie FM, Oliver JS: Detection of benzodiazepines in hair using ELISA and LC-ESI-MS-MS. J Anal Toxicol. 2006 Sep;30(7):441-8. [PubMed:16959136]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
Gene Name
UGT2B15
Uniprot ID
P54855
Uniprot Name
UDP-glucuronosyltransferase 2B15
Molecular Weight
61035.815 Da
References
  1. Chung JY, Cho JY, Yu KS, Kim JR, Jung HR, Lim KS, Jang IJ, Shin SG: Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clin Pharmacol Ther. 2005 Jun;77(6):486-94. [PubMed:15961980]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
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. Gregor KJ, Way K, Young CH, James SP: Concomitant use of selective serotonin reuptake inhibitors with other cytochrome P450 2D6 or 3A4 metabolized medications: how often does it really happen? J Affect Disord. 1997 Oct;46(1):59-67. [PubMed:9387087]
  2. Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [PubMed:18175099]
  3. Benzodiazepine metabolism and pharmacokinetic [Link]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 17:04