Identification
- Summary
Lorazepam is a short-acting benzodiazepine commonly used to treat panic disorders, severe anxiety, and seizures.
- Brand Names
- Ativan, Loreev
- Generic Name
- Lorazepam
- DrugBank Accession Number
- DB00186
- Background
Lorazepam is a short-acting and rapidly cleared benzodiazepine used commonly as a sedative and anxiolytic.6 It was developed by DJ Richards, presented and marketed initially by Wyeth Pharmaceuticals in the USA in 1977. The first historic FDA label approval is reported in 1985 by the company Mutual Pharm.15
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lorazepam (DB00186)
- Weight
- Average: 321.158
Monoisotopic: 320.011932988 - Chemical Formula
- C15H10Cl2N2O2
- Synonyms
- Loracepam
- Lorazepam
- o-Chlorooxazepam
- o-Chloroxazepam
- External IDs
- WY-4036
Pharmacology
- Indication
Lorazepam is FDA-approved for the short-term relief of anxiety symptoms related to anxiety disorders and anxiety associated with depressive symptoms such as anxiety-associated insomnia. It is as well used as an anesthesia premedication in adults to relieve anxiety or to produce sedation/amnesia and for the treatment of status epilepticus.12
Some off-label indications of lorazepam include rapid tranquilization of an agitated patient, alcohol withdrawal delirium, alcohol withdrawal syndrome, muscle spasms, insomnia, panic disorder, delirium, chemotherapy-associated anticipatory nausea and vomiting, and psychogenic catatonia.12
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Agitation ••• ••••• Treatment of Alcohol withdrawal delirium ••• ••••• Treatment of Alcohol withdrawal syndrome(aws) ••• ••••• Symptomatic treatment of Anxiety •••••••••••• •••••••••••• •••••• Management of Anxiety •••••••••••• •••••••••••• ••••••• ••••••••• •••••• - Associated Therapies
- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
The effect of lorazepam in GABA-A receptors produces an increase in the frequency of opening of the chloride ion channel. However, for its effect to generate, the neurotransmitter is required.8 The anticonvulsant properties of lorazepam are thought to be related to the binding to voltage-dependent sodium channels in which the sustained repetitive firing gets limited by the slow recovery of sodium channels due to the benzodiazepine effect.9
The effect of lorazepam seems to be very compartmental which was observed with a different generation of sleepiness and a dizziness effect.10
- Mechanism of action
Lorazepam allosterically binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane.12
According to the binding site of lorazepam, we can observe different activities as the binding in the amygdala is known to help mainly in anxiety disorders while the binding in the cerebral cortex helps in seizure disorders.12
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - Absorption
Readily absorbed with an absolute bioavailability of 90% when given orally. When intramuscularly administered a dose of 4 mg, lorazepam is completely and rapidly absorbed and achieves a maximal serum concentration of 48 ng/ml in 15-30 minutes. When administered orally, the time to attained maximum concentration is observed to be of 2 hours.12
- Volume of distribution
The reported volume of distribution of lorazepam is 1.3 L/kg.13 It is important to mention that due to the lipophilicity of lorazepam, it does not redistribute as fast in the brain.14
- Protein binding
Reports indicate that 85% of lorazepam administered dose is protein bound.13
- Metabolism
Lorazepam is hepatically metabolized by CYP450 isoenzymes and extensively conjugated to the 3-0-phenolic glucuronide.12 This is an inactive metabolite and is eliminated mainly by the kidneys.
Hover over products below to view reaction partners
- Route of elimination
When a single 2 mg oral dose is given to healthy subjects, 88% of the administered dose is recovered in urine and 7% was recovered in feces. From the excreted dose in urine, the major form is the glucuronide version that represents 74% while only 0.3% of the dose is recovered as unchanged lorazepam.13
- Half-life
When administered parentally, the registered half-life of lorazepam is of 14 hours.12 Following the administration of 1 mg of lorazepam in healthy adult male volunteers and using a multi-doses equation based on a one-compartment model, the average elimination half-life of lorazepam was estimated to be 11 hours and 8 hours for sublingual and oral doses respectively.11 The absorption half-life was calculated to be 55 minutes for oral doses and 15 minutes for sublingual doses.11
- Clearance
In vivo studies with lorazepam have shown a clearance rate of 5.8 ml.min/kg.7
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
The LD50 observed by oral administration in a mouse is of 1850 mg/kg.16 When an overdose administration is registered, signs of CNS and respiratory depression are rapidly observed. An overdose stage can result in profound sedation, deep respiratory depression, coma, and death.12 When overdose is observed, it is recommended to administer emergency symptomatic medical support with attention to produce an increase in lorazepam elimination.13
There is no evidence of carcinogenicity nor mutagenicity. At doses higher than 40 mg/kg there is evidence of fetal resorption and increase in fetal loss.Label
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Lorazepam is combined with 1,2-Benzodiazepine. Abacavir Lorazepam may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Lorazepam can be increased when it is combined with Abametapir. Aceclofenac Aceclofenac may decrease the excretion rate of Lorazepam which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Lorazepam which could result in a higher serum level. - Food Interactions
- Avoid alcohol.
- Limit caffeine intake.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Images
- International/Other Brands
- Almazine (Psyco Remedies) / Anxiedin (U-Liang) / Idalprem (Novartis) / Lorabenz / Lorsilan (Belupo) / Somagerol / Temesta (Wyeth) / Wypax (Wyeth KK)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ativan Injection 2.0 mg/1mL Intramuscular; Intravenous Hikma Pharmaceuticals USA Inc. 1980-07-25 Not applicable US 
Ativan Tablet 1 mg/1 Oral Physicians Total Care, Inc. 2010-03-16 2012-06-30 US Ativan Tablet 1 mg Oral Pfizer Canada Ulc 1994-12-31 Not applicable Canada 
Ativan Tablet 0.5 mg/1 Oral BTA Pharmaceuticals Inc. 2010-03-16 2015-01-31 US Ativan Tablet 1 mg Sublingual Pfizer Canada Ulc 1994-12-31 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-lorazepam Tablet 0.5 mg Oral Apotex Corporation 1985-12-31 Not applicable Canada Apo-lorazepam Tablet 2 mg Oral Apotex Corporation 1985-12-31 Not applicable Canada Apo-lorazepam Tablet 1 mg Oral Apotex Corporation 1985-12-31 Not applicable Canada Dom-lorazepam Tablet .5 mg Oral Dominion Pharmacal 2002-04-25 2019-02-20 Canada Dom-lorazepam Tablet 2 mg Oral Dominion Pharmacal 2002-04-25 2019-02-20 Canada
Categories
- ATC Codes
- N05BA56 — Lorazepam, combinationsN05BA06 — Lorazepam
- Drug Categories
- Anti-Anxiety Agents
- Anticonvulsants
- Antiemetics
- Autonomic Agents
- Benzazepines
- Benzodiazepine hypnotics and sedatives
- Benzodiazepines and benzodiazepine derivatives
- Benzodiazepinones
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- GABA Agents
- GABA Modulators
- Gastrointestinal Agents
- Heterocyclic Compounds, Fused-Ring
- Hypnotics and Sedatives
- Muscle Relaxants
- Muscle Relaxants, Centrally Acting Agents
- Nervous System
- Neurotransmitter Agents
- Peripheral Nervous System Agents
- Psycholeptics
- Psychotropic Drugs
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- 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 / Alkanolamine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group show 19 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- O26FZP769L
- CAS number
- 846-49-1
- 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
References
- Synthesis Reference
Igor Lifshitz, "Process for preparing pure crystalline lorazepam." U.S. Patent US20010039340, issued November 08, 2001.
US20010039340- General References
- 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. [Article]
- Lader M: Short-term versus long-term benzodiazepine therapy. Curr Med Res Opin. 1984;8 Suppl 4:120-6. [Article]
- 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. [Article]
- 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. [Article]
- Milligan DW, Howard MR, Judd A: Premedication with lorazepam before bone marrow biopsy. J Clin Pathol. 1987 Jun;40(6):696-8. [Article]
- Authors unspecified: Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. Br Med J. 1980 Mar 29;280(6218):910-2. [Article]
- Li C, Liu T, Cui X, Uss AS, Cheng KC: Development of in vitro pharmacokinetic screens using Caco-2, human hepatocyte, and Caco-2/human hepatocyte hybrid systems for the prediction of oral bioavailability in humans. J Biomol Screen. 2007 Dec;12(8):1084-91. doi: 10.1177/1087057107308892. Epub 2007 Nov 7. [Article]
- 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. [Article]
- McLean MJ, Macdonald RL: Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture. J Pharmacol Exp Ther. 1988 Feb;244(2):789-95. [Article]
- Kamal MA, Smith DE, Cook J, Feltner D, Moton A, Ouellet D: Pharmacodynamic differentiation of lorazepam sleepiness and dizziness using an ordered categorical measure. J Pharm Sci. 2010 Aug;99(8):3628-41. doi: 10.1002/jps.22093. [Article]
- Caille G, Spenard J, Lacasse Y, Brennan J: Pharmacokinetics of two lorazepam formulations, oral and sublingual, after multiple doses. Biopharm Drug Dispos. 1983 Jan-Mar;4(1):31-42. doi: 10.1002/bdd.2510040106. [Article]
- Ghiasi N. and Marwaha R. (2018). Lorazepam.. Treasure Island, FL.
- Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
- Volpe J. (2008). Neurology of the Newborn (5th ed.). Saunders Elsevier.
- FDA approvals [Link]
- Lorazepam monograph [Link]
- FDA Approved Drug Products: Ativan (lorazepam) for intravenous or intramuscular injection [Updated 01/2023] [Link]
- FDA Approved Drug Products: Ativan (lorazepam) tablets for oral administration [Updated 01/2023] [Link]
- External Links
- Human Metabolome Database
- HMDB0014332
- KEGG Drug
- D00365
- PubChem Compound
- 3958
- PubChem Substance
- 46508468
- ChemSpider
- 3821
- BindingDB
- 50292627
- 6470
- ChEBI
- 6539
- ChEMBL
- CHEMBL580
- Therapeutic Targets Database
- DAP000237
- PharmGKB
- PA450267
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lorazepam
- FDA label
- Download (540 KB)
- MSDS
- Download (81.8 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Diagnostic Anxiety Disorders / Generalized Anxiety Disorder 1 4 Completed Other Cognitive Deficits 1 4 Completed Other Healthy Subjects (HS) 1 4 Completed Treatment Agitation 1 4 Completed Treatment Alcohol Dependency 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
Form Route Strength Injection Intramuscular; Intravenous 4.0 mg/1mL Tablet Oral 0.5 mg Tablet Sublingual 0.5 mg Tablet Sublingual 1 mg Tablet Sublingual 2 mg Tablet Oral 2 mg Liquid Intramuscular; Intravenous 4 mg / mL Solution Intramuscular; Intravenous 4 mg / mL Tablet Oral .5 mg / tab Tablet Oral 1 mg / tab Tablet Oral 2 mg / tab Tablet Oral 1 mg Solution / drops Oral Concentrate Oral 2 mg/1mL Injection Intramuscular 2 mg/1mL Injection Intramuscular; Intravenous 2 mg/1mL Injection Intramuscular; Intravenous 2.0 mg/1mL Injection Intramuscular; Intravenous 4 mg/1mL Injection, solution Intramuscular; Intravenous 2 mg/1mL Injection, solution Intramuscular; Intravenous 4 mg/1mL Liquid Oral 2 mg/1mL Solution, concentrate Oral 2 mg/1mL Tablet Oral Tablet Oral .5 mg/1 Tablet Oral 0.5 mg/1 Tablet Oral 1 mg/1 Tablet Oral 1.0 mg Tablet Oral 2 mg/1 Tablet Oral 2.0 mg Tablet, film coated Oral Tablet Oral 2.099 mg Tablet, orally disintegrating Oral 1 MG Tablet, orally disintegrating Oral 2.5 MG Tablet, orally disintegrating Oral Tablet Tablet, film coated Oral 1 MG Tablet, film coated Oral 2.5 MG Solution Intramuscular; Intravenous 2 mg / mL Injection, solution 4 MG/ML Injection, solution Parenteral Capsule, extended release Oral 1 mg/1 Capsule, extended release Oral 1.5 mg/1 Capsule, extended release Oral 2 mg/1 Capsule, extended release Oral 3 mg/1 Solution Parenteral 1.00 mg Tablet Oral 2.000 mg Tablet Oral .5 mg Tablet Oral 1.000 mg Tablet Oral 0.5 mg / tab Capsule Oral 1.0000 mg Injection, solution Parenteral 4 MG/ML Solution / drops Oral 2 MG/ML Tablet 1 MG Tablet 2.5 MG Tablet 0.5 mg Tablet Oral 2.5 mg Tablet 2 mg Injection, solution Intramuscular; Intravenous 2 mg/ml - Prices
Unit description Cost Unit LORazepam Intensol 2 mg/ml Concentrate 30ml Bottle 44.99USD bottle Lorazepam powder 20.81USD g Lorazepam 4 mg/ml vial 9.59USD ml Lorazepam 2 mg/ml vial 2.5USD ml Ativan 2 mg tablet 2.3USD tablet Ativan 4 mg/ml vial 2.16USD ml Ativan 1 mg tablet 1.96USD tablet Lorazepam intensol 2 mg/ml 1.6USD ml Lorazepam-ns 60 mg/60 ml bag 1.53USD ml Ativan 0.5 mg tablet 1.37USD tablet Lorazepam-d5w 100 mg/100 ml 1.16USD ml Lorazepam-ns 100 mg/100 ml bag 1.16USD ml Lorazepam 2 mg tablet 1.01USD tablet Ativan 2 mg/ml vial 0.9USD ml Lorazepam 1 mg tablet 0.69USD tablet Lorazepam 0.5 mg tablet 0.55USD tablet Ativan 2 mg Sublingual Tablet 0.24USD tablet Ativan 1 mg Sublingual Tablet 0.15USD tablet Ativan 0.5 mg Sublingual Tablet 0.12USD tablet Apo-Lorazepam 2 mg Tablet 0.07USD tablet Novo-Lorazem 2 mg Tablet 0.07USD tablet Pms-Lorazepam 2 mg Tablet 0.07USD tablet Apo-Lorazepam 1 mg Tablet 0.05USD tablet Novo-Lorazem 1 mg Tablet 0.05USD tablet Pms-Lorazepam 1 mg Tablet 0.05USD tablet Apo-Lorazepam 0.5 mg Tablet 0.04USD tablet Novo-Lorazem 0.5 mg Tablet 0.04USD tablet Pms-Lorazepam 0.5 mg Tablet 0.04USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8999393 No 2015-04-07 2034-01-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 192-194 British Patent 1,022,642. boiling point (°C) 533.8 ºC at 760 mm Hg Chemspider water solubility 80 mg/L MERCK INDEX (1996) logP 2.39 HANSCH,C ET AL. (1995) logS -3.6 ADME Research, USCD Caco2 permeability 200 Li C., Liu T., Ciu X., Uss A. and Cheng K. (2007). Society of Biomolecular Science. pKa 13 MERCK INDEX (1996); pK1 - Predicted Properties
Property Value Source Water Solubility 0.0176 mg/mL ALOGPS logP 2.98 ALOGPS logP 3.53 Chemaxon logS -4.3 ALOGPS pKa (Strongest Acidic) 10.61 Chemaxon pKa (Strongest Basic) -2.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 61.69 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 82.7 m3·mol-1 Chemaxon Polarizability 30.33 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9826 Blood Brain Barrier + 0.9641 Caco-2 permeable + 0.8867 P-glycoprotein substrate Substrate 0.517 P-glycoprotein inhibitor I Non-inhibitor 0.8866 P-glycoprotein inhibitor II Non-inhibitor 0.9167 Renal organic cation transporter Non-inhibitor 0.8812 CYP450 2C9 substrate Non-substrate 0.7692 CYP450 2D6 substrate Non-substrate 0.8685 CYP450 3A4 substrate Substrate 0.5631 CYP450 1A2 substrate Inhibitor 0.8262 CYP450 2C9 inhibitor Non-inhibitor 0.5063 CYP450 2D6 inhibitor Non-inhibitor 0.8445 CYP450 2C19 inhibitor Inhibitor 0.5065 CYP450 3A4 inhibitor Non-inhibitor 0.6563 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6407 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.7711 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.8229 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.999 hERG inhibition (predictor II) Non-inhibitor 0.8734
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 167.9812264 predictedDarkChem Lite v0.1.0 [M-H]- 164.1689 predictedDeepCCS 1.0 (2019) [M+H]+ 168.1819264 predictedDarkChem Lite v0.1.0 [M+H]+ 166.5269 predictedDeepCCS 1.0 (2019) [M+Na]+ 168.0985264 predictedDarkChem Lite v0.1.0 [M+Na]+ 172.62006 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Positive allosteric modulator
- Curator comments
- The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.
- 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
- 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. [Article]
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.
- 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
- Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]
- Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Olkkola KT, Ahonen J: Midazolam and other benzodiazepines. Handb Exp Pharmacol. 2008;(182):335-60. doi: 10.1007/978-3-540-74806-9_16. [Article]
- Benzodiazepine metabolism and pharmacokinetic [Link]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55