Identification
- Summary
Delorazepam is a benzodiazepine used to manage severe anxiety disorders and insomnia.
- Generic Name
- Delorazepam
- DrugBank Accession Number
- DB01511
- Background
Delorazepam is a benzodiazepine which, like other drugs in its class, possesses anxiolytic, skeletal muscle relaxant, hypnotic and anticonvulsant properties. It may have adverse effects such as drowsiness, and cognitive impairments such as short term memory impairment.
Delorazepam is an active metabolite of the benzodiazepine known as cloxazolam. It is a long acting benzodiazepine which makes it superior in this sense to lorazepam which is short acting. Lorazepam is also a major active metabolite of delorazepam.
In addition to be long acting, delorazepam is relatively potent, with 1 mg of delorazepam being the equivalent of 10 mg diazepam. It has been approved for marketing in Italy.
- Type
- Small Molecule
- Groups
- Experimental, Illicit
- Structure
Structure for Delorazepam (DB01511)
- Weight
- Average: 305.159
Monoisotopic: 304.017018366 - Chemical Formula
- C15H10Cl2N2O
- Synonyms
- Chlordesmethyldiazepam
- Clordesmetildiazepam
- Delorazepam
- Delorazepamum
- External IDs
- Ro 5-3027
- RV-12165
Pharmacology
- Indication
Mainly used as an anti-anxiety agent. Studies have found delorazepam to be more effective in the first 4 weeks of use than antidepressants; however, after 4 weeks, antidepressants showed superior anti-anxiety effects. Anti-anxiety effects also appear to be weaker in elderly patients.
Effectiveness has also been observed in the treatment of alcohol withdrawal. Delorazapam was reported to be a manageable drug in that it did not exhibit severe side effects and did not require further therapies to control symptoms of withdrawal.
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 Treatment of Anxiety •••••••••••• •••••••••• •••••••• Treatment of Anxiety •••••••••••• ••••••••• •••••• Treatment of Epilepsies •••••••••••• •••••••••• •••••••• Treatment of Insomnia •••••••••••• ••••••••• •••••• Treatment of Sleep disorder •••••••••••• •••••••••• •••••••• - 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
Not Available
- Mechanism of action
Target Actions Organism AGABA(A) Receptor positive allosteric modulatorHumans AGABA(A) Receptor Benzodiazepine Binding Site ligandHumans - Absorption
77-87% oral bioavailability, with a relatively slow absorption rate. Reaches peak plasma levels within 1-2 hours of administration. Food may slow absorption, however other pharmacokinetic variables remain unchanged. After multiple doses delorazepam accumulates, although accumulation is slower in younger patients.
- Volume of distribution
140 L/kg apparent volume of distribution in 11 patients with normal renal function; 47 L/kg in 11 patients with renal failure and on regular hemodialysis.
In another study, apparent volume of distribution was 65 L/kg in 8 patients with liver disease and 118.4 L/kg in 12 healthy controls.
- Protein binding
>90% protein bound.
- Metabolism
Delorazepam is metabolized at a relatively slow pace by the liver. The major metabolite (15-34% of the parent drug) is lorazepam. Older patients metabolize delorazepam slower than younger patients.
- Route of elimination
Renally eliminated.
- Half-life
Very long elimination half life of 80-115 hours, varying with age. Elimination is slower as age increases. [1] Liver disease also impacts elimination half life, with impairment resulting in half lives up to 395 hours.
- Clearance
Still detectable 72 hours after dosing in healthy patients. Patients with liver disease experienced a reduction in clearance from 0.13 to 0.25 ng/mLh.
- Adverse Effects
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Older patients metabolize delorazepam slower than younger patients and thus suffer from more adverse effects.
- 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 Delorazepam is combined with 1,2-Benzodiazepine. Acetazolamide The risk or severity of CNS depression can be increased when Acetazolamide is combined with Delorazepam. Acetophenazine The risk or severity of CNS depression can be increased when Acetophenazine is combined with Delorazepam. Agomelatine The risk or severity of CNS depression can be increased when Delorazepam is combined with Agomelatine. Alfentanil The risk or severity of adverse effects can be increased when Alfentanil is combined with Delorazepam. - Food Interactions
- Not Available
Products
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- Delorazepam Almus (Almus) / Delorazepam Alter (Alter) / Delorazepam Aurobindo (Aurobindo) / Delorazepam DOC (DOC Generici) / Delorazepam EG (EG) / Delorazepam Germed (Germed Pharma) / Delorazepam Hexal (Hexal) / Delorazepam Mylan (Mylan) / Delorazepam Pensa (Pensa Pharma) / Delorazepam Ranbaxy (Ranbaxy Italia) / Delorazepam ratiopharm (Ratiopharm Italia) / Delorazepam Sandoz (Sandoz) / Delorazepam Teva (Teva Italia,) / Delorazepam Winthrop (Sanofi Winthrop) / EN (Abbott)
Categories
- Drug Categories
- 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 / Organopnictogen compounds / Organochlorides show 3 more
- Substituents
- 1,4-benzodiazepine / Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- O91W32476G
- CAS number
- 2894-67-9
- InChI Key
- CHIFCDOIPRCHCF-UHFFFAOYSA-N
- InChI
- InChI=1S/C15H10Cl2N2O/c16-9-5-6-13-11(7-9)15(18-8-14(20)19-13)10-3-1-2-4-12(10)17/h1-7H,8H2,(H,19,20)
- IUPAC Name
- 7-chloro-5-(2-chlorophenyl)-2,3-dihydro-1H-1,4-benzodiazepin-2-one
- SMILES
- ClC1=CC2=C(NC(=O)CN=C2C2=CC=CC=C2Cl)C=C1
References
- General References
- Bareggi SR, Nielsen NP, Leva S, Pirola R, Zecca L, Lorini M: Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam). Int J Clin Pharmacol Res. 1986;6(4):309-14. [Article]
- Bareggi SR, Pirola R, Potvin P, Devis G: Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam. Eur J Clin Pharmacol. 1995;48(3-4):265-8. [Article]
- Cazzato G, Gioseffi M, Torre P, Coppola N: [Prevention and therapy of delirium tremens with tiapride and chlordesmethyldiazepam]. Riv Neurol. 1982 Nov-Dec;52(6):331-42. [Article]
- Scarone S, Strambi LF, Cazzullo CL: Effects of two dosages of chlordesmethyldiazepam on mnestic-information processes in normal subjects. Clin Ther. 1981;4(3):184-91. [Article]
- Sennesael J, Verbeelen D, Vanhaelst L, Pirola R, Bareggi SR: Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis. Eur J Clin Pharmacol. 1991;41(1):65-8. [Article]
- External Links
- KEGG Drug
- D07784
- PubChem Compound
- 17925
- PubChem Substance
- 46504957
- ChemSpider
- 16929
- BindingDB
- 50026858
- ChEBI
- 135295
- ChEMBL
- CHEMBL268254
- ZINC
- ZINC000001255325
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Delorazepam
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 Not Available Completed Treatment Anorexia Nervosa (AN) / Bulimia Nervosa 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 0.5 MG Tablet Oral 1 MG Tablet Oral 2 MG Solution / drops Oral 1 MG/ML Solution / drops Oral Tablet Oral Injection, solution Intramuscular; Intravenous 0.5 MG/1ML Injection, solution Intramuscular; Intravenous 1 MG/ML Injection, solution Intramuscular; Intravenous 2 MG/1ML Injection, solution Intramuscular; Intravenous 5 MG/1ML - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 3.15 HANSCH,C & LEO,AJ (1985) - Predicted Properties
Property Value Source Water Solubility 0.00642 mg/mL ALOGPS logP 3.46 ALOGPS logP 3.82 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 12.29 Chemaxon pKa (Strongest Basic) 2.05 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 41.46 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 81.5 m3·mol-1 Chemaxon Polarizability 29.44 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 + 1.0 Blood Brain Barrier + 0.9928 Caco-2 permeable + 0.8835 P-glycoprotein substrate Substrate 0.5944 P-glycoprotein inhibitor I Non-inhibitor 0.7784 P-glycoprotein inhibitor II Non-inhibitor 0.9457 Renal organic cation transporter Non-inhibitor 0.5927 CYP450 2C9 substrate Non-substrate 0.7891 CYP450 2D6 substrate Non-substrate 0.9139 CYP450 3A4 substrate Substrate 0.7492 CYP450 1A2 substrate Inhibitor 0.9347 CYP450 2C9 inhibitor Inhibitor 0.5 CYP450 2D6 inhibitor Non-inhibitor 0.7822 CYP450 2C19 inhibitor Inhibitor 0.7114 CYP450 3A4 inhibitor Non-inhibitor 0.7519 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6921 Ames test Non AMES toxic 0.9163 Carcinogenicity Non-carcinogens 0.7766 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.1516 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9954 hERG inhibition (predictor II) Non-inhibitor 0.8771
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 162.2707 predictedDeepCCS 1.0 (2019) [M+H]+ 164.66628 predictedDeepCCS 1.0 (2019) [M+Na]+ 170.68677 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- 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
- 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]
Drug created at July 31, 2007 13:10 / Updated at May 05, 2021 20:30