Delorazepam

Identification

Name
Delorazepam
Accession Number
DB01511
Type
Small Molecule
Groups
Experimental, Illicit
Description

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. [4]

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.

Structure
Thumb
Synonyms
  • Chlordesmethyldiazepam
International/Other Brands
Dadumir / 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
UNII
O91W32476G
CAS number
2894-67-9
Weight
Average: 305.159
Monoisotopic: 304.017018366
Chemical Formula
C15H10Cl2N2O
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

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. [Wikipedia] Anti-anxiety effects also appear to be weaker in elderly patients. [1]

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. [3]

Pharmacodynamics
Not Available
Mechanism of action
Not Available
Absorption

77-87% oral bioavailability, with a relatively slow absorption rate. [5] 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, however accumulation is slower in younger patients.[1]

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. [5]

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. [2]

Protein binding

>90% protein bound. [5]

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. [1]

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. [2]

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. [2]

Toxicity

Older patients metabolize delorazepam slower than younger patients and thus suffer from more adverse effects. [1]

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcetazolamideThe risk or severity of adverse effects can be increased when Delorazepam is combined with Acetazolamide.
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Delorazepam.
AlimemazineThe risk or severity of adverse effects can be increased when Delorazepam is combined with Alimemazine.
AlmotriptanThe risk or severity of adverse effects can be increased when Delorazepam is combined with Almotriptan.
AlosetronThe risk or severity of adverse effects can be increased when Delorazepam is combined with Alosetron.
AlprazolamThe risk or severity of adverse effects can be increased when Alprazolam is combined with Delorazepam.
Ambroxol acefyllinateThe therapeutic efficacy of Delorazepam can be decreased when used in combination with Ambroxol acefyllinate.
AmikacinThe risk or severity of adverse effects can be increased when Delorazepam is combined with Amikacin.
AminophyllineThe therapeutic efficacy of Delorazepam can be decreased when used in combination with Aminophylline.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Delorazepam.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:2875955]
  2. 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. [PubMed:7589052]
  3. 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. [PubMed:6130594]
  4. 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. [PubMed:6796270]
  5. 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. [PubMed:1782980]
External Links
KEGG Drug
D07784
PubChem Compound
17925
PubChem Substance
46504957
ChemSpider
16929
BindingDB
50026858
ChEBI
135295
ChEMBL
CHEMBL268254
Drugs.com
Drugs.com Drug Page
Wikipedia
Delorazepam

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedTreatmentAnorexia Nervosa (AN) / Bulimia Nervosa (BN)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.15HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
Water Solubility0.00642 mg/mLALOGPS
logP3.46ALOGPS
logP3.82ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)12.29ChemAxon
pKa (Strongest Basic)2.05ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.46 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity81.5 m3·mol-1ChemAxon
Polarizability29.44 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9928
Caco-2 permeable+0.8835
P-glycoprotein substrateSubstrate0.5944
P-glycoprotein inhibitor INon-inhibitor0.7784
P-glycoprotein inhibitor IINon-inhibitor0.9457
Renal organic cation transporterNon-inhibitor0.5927
CYP450 2C9 substrateNon-substrate0.7891
CYP450 2D6 substrateNon-substrate0.9139
CYP450 3A4 substrateSubstrate0.7492
CYP450 1A2 substrateInhibitor0.9347
CYP450 2C9 inhibitorInhibitor0.5
CYP450 2D6 inhibitorNon-inhibitor0.7822
CYP450 2C19 inhibitorInhibitor0.7114
CYP450 3A4 inhibitorNon-inhibitor0.7519
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6921
Ames testNon AMES toxic0.9163
CarcinogenicityNon-carcinogens0.7766
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.1516 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9954
hERG inhibition (predictor II)Non-inhibitor0.8771
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
GC-MS Spectrum - EI-BGC-MSsplash10-0fb9-6794000000-90a56d756980bc170dc2
Mass Spectrum (Electron Ionization)MSsplash10-0fb9-3594000000-3da2aad1da4843c38183
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

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 / Organopnictogen compounds / Organochlorides
show 3 more
Substituents
1,4-benzodiazepine / Alpha-amino acid or derivatives / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Benzenoid / Carboxamide group / Ketimine
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on July 31, 2007 07:10 / Updated on October 01, 2018 13:05