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Identification
NameDelorazepam
Accession NumberDB01511
Typesmall molecule
Groupsapproved, 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. [Wikipedia] It has been approved for marketing in Italy.

Structure
Thumb
Synonyms
SynonymLanguageCode
CDDZNot AvailableNot Available
ChlordesmethyldiazepamNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Dadumir Not Available
Delorazepam AlmusAlmus
Delorazepam AlterAlter
Delorazepam AurobindoAurobindo
Delorazepam DOCDOC Generici
Delorazepam EGEG
Delorazepam GermedGermed Pharma
Delorazepam HexalHexal
Delorazepam MylanMylan
Delorazepam PensaPensa Pharma
Delorazepam RanbaxyRanbaxy Italia
Delorazepam ratiopharmRatiopharm Italia
Delorazepam SandozSandoz
Delorazepam TevaTeva Italia,
Delorazepam WinthropSanofi Winthrop
ENAbbott
Brand mixturesNot Available
Categories
CAS number2894-67-9
WeightAverage: 305.159
Monoisotopic: 304.017018366
Chemical FormulaC15H10Cl2N2O
InChI KeyInChIKey=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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzodiazepines
SubclassNot Available
Direct parentBenzodiazepines
Alternative parentsChlorobenzenes; Aryl Chlorides; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Organochlorides
Substituentschlorobenzene; benzene; aryl chloride; aryl halide; secondary carboxylic acid amide; carboxamide group; polyamine; carboxylic acid derivative; carboxylic acid; organochloride; organohalogen; organonitrogen compound
Classification descriptionThis compound belongs to the benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).
Pharmacology
IndicationMainly 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]
PharmacodynamicsNot Available
Mechanism of actionNot Available
Absorption77-87% 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 eliminationRenally eliminated.
Half lifeVery 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

ToxicityOlder patients metabolize delorazepam slower than younger patients and thus suffer from more adverse effects. [1]
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Inhibitor 0.5
CYP450 2D6 substrate Non-inhibitor 0.7822
CYP450 2C19 substrate Inhibitor 0.7114
CYP450 3A4 substrate 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP3.15HANSCH,C & LEO,AJ (1985)
Predicted Properties
PropertyValueSource
water solubility6.42e-03 g/lALOGPS
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 area41.46ChemAxon
rotatable bond count1ChemAxon
refractivity81.5ChemAxon
polarizability29.44ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference

1. Bareggi, S. R., et al. “Age-related multiple-dose pharmacokinetics and anxiolytic effects of delorazepam (chlordesmethyldiazepam).” International journal of clinical pharmacology research 6.4 (1986): 309.

2. Bareggi, S. R., et al. “Effects of liver disease on the pharmacokinetics of intravenous and oral chlordesmethyldiazepam.” European journal of clinical pharmacology 48.3-4 (1995): 265-268.

3. Cazzato, G., et al. “[Prevention and therapy of delirium tremens with tiapride and chlordesmethyldiazepam].” Rivista di neurologia 52.6 (1981): 331-342.

4. Scarone, S., L. F. Strambi, and C. L. Cazzullo. “Effects of two dosages of chlordesmethyldiazepam on mnestic-information processes in normal subjects.” Clinical therapeutics 4.3 (1981): 184.

5. Sennesael, J., et al. “Pharmacokinetics of intravenous and oral chlordesmethyldiazepam in patients on regular haemodialysis.” European journal of clinical pharmacology 41.1 (1991): 65-68.

External Links
ResourceLink
KEGG DrugD07784
PubChem Compound17925
PubChem Substance46504957
ChemSpider16929
BindingDB50026858
Drugs.comhttp://www.drugs.com/international/delorazepam.html
WikipediaDelorazepam
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
Comments
Drug created on July 31, 2007 07:10 / Updated on January 02, 2014 14:26