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    Delorazepam molecular structure

    Delorazepam Stats & Data

    En Dadumir Nordiclazepam Chlordesmethyldiazepam
    NPS DataHub
    MW305.16
    FormulaC15H10Cl2N2O
    CAS2894-67-9
    IUPAC7-chloro-5-(2-chlorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
    SMILESO=C1CN=C(c2ccccc2Cl)c2cc(Cl)ccc2N1
    InChIKeyCHIFCDOIPRCHCF-UHFFFAOYSA-N
    2020/3. Benzodiazepine; 2021/3. Benzodiazepine; 2022/3. Benzodiazepine
    Chemical Class Benzodiazepine
    Psychoactive Class Depressant

    Pharmacology

    DrugBank
    Protein binding >90% protein bound. State Solid

    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. 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.

    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.

    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.

    Toxicity

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

    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.

    Half-life

    Very long elimination half life of 80-115 hours, varying with age. Elimination is slower as age increases. Liver disease also impacts elimination half life, with impairment resulting in half lives up to 395 hours.

    Elimination

    Renally eliminated.

    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.

    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.

    Receptor Profile

    Receptor Actions

    Modulators
    GABA-A receptor positive allosteric modulator (benzodiazepine site)

    History & Culture

    Delorazepam is an uncommon benzodiazepine that has been marketed primarily in Italy, where it is available under the trade name EN. The compound is notable for its relationship to other benzodiazepines in this class, serving as an active metabolite of both diclazepam and cloxazolam. As a derivative of desmethyldiazepam, it shares structural similarities with several other members of the benzodiazepine family. Despite its limited international availability compared to more widely prescribed benzodiazepines, delorazepam has found clinical application in Italy for anxiety-related conditions, including its use as a premedication for patients experiencing dental phobia.

    Effect Profile

    Curated
    Benzodiazepine 7.1

    Strong anxiolysis, cognitive impairment, and euphoria with mild sedation

    Anxiolysis×3
    10
    Sedation / Relaxation×2
    5
    Motor / Cognitive Impairment×1
    10
    Euphoria / Mood Lift×1
    10

    Tolerance & Pharmacokinetics

    drugs.wiki

    Tolerance Decay

    Full tolerance 3d Half tolerance 37d Baseline ~60d
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