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    Halazepam molecular structure

    Halazepam Stats & Data

    Paxipam Alapryl Pacinone
    NPS DataHub
    MW352.74
    FormulaC17H12ClF3N2O
    CAS23092-17-3
    IUPAC7-chloro-5-phenyl-1-(2,2,2-trifluoroethyl)-3H-1,4-benzodiazepin-2-one
    SMILESFC(F)(F)CN1C(=O)CN=C(c2ccccc2)c2cc(Cl)ccc12
    InChIKeyWYCLKVQLVUQKNZ-UHFFFAOYSA-N
    2020/3. Benzodiazepine; 2021/3. Benzodiazepine; 2022/3. Benzodiazepine
    Chemical Class Benzodiazepine
    Psychoactive Class Depressant
    Half-Life Parent (halazepam): short-to-intermediate; Active metabolite (desmethyldiazepam/nordazepam): ~30-200 hours with wide interindividual variability.

    Pharmacology

    DrugBank
    State Solid Metabolism Hepatic.

    Description

    Halazepam is a _benzodiazepine_ derivative drug exerting anxiolytic, anticonvulsant, sedative, a muscle relaxing effects. It has been shown to be less toxic than chlordiazepoxide or diazepam. This drug is no longer marketed in the United States, and was withdrawn by _Schering_, its manufacturer, in 2009.

    Mechanism of Action

    Benzodiazepines bind nonspecifically to benzodiazepine receptors BNZ1, which mediates sleep, and BNZ2, which affects affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. As benzodiazepine receptors are thought to be coupled to gamma-aminobutyric acid-A (GABAA) receptors, this enhances the effects of GABA by increasing GABA affinity for the GABA receptor. Binding of GABA to the site opens the chloride channel, resulting in a hyperpolarized cell membrane that prevents further excitation of the cell.

    Indication

    Used to relieve anxiety, nervousness, and tension associated with anxiety disorders.

    Receptor Profile

    Receptor Actions

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

    Receptor Binding

    Translocator protein modulator

    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
    Half-Life
    Parent (halazepam): short-to-intermediate; Active metabolite (desmethyldiazepam/nordazepam): ~30-200 hours with wide interindividual variability.
    Addiction Potential
    Moderate to high, consistent with benzodiazepines; risk of tolerance, dependence, and withdrawal with repeated use or high doses.

    Tolerance Decay

    Full tolerance 14d Half tolerance 14d Baseline ~60d

    Sedative and anticonvulsant effects exhibit rapid tolerance with repeated dosing over days to weeks, similar to other benzodiazepines. Cross-tolerance is substantial across benzodiazepines and extends partially to other GABAergic sedatives (alcohol, barbiturates, Z-drugs). Tolerance generally recedes gradually over weeks to months of abstinence; individual variability is large. Data quality is limited; values are heuristic to support harm reduction, not precise pharmacometrics.

    Cross-Tolerances

    Benzodiazepines (class)
    100% ●●●
    Alcohol (ethanol)
    30% ●○○
    Barbiturates
    50% ●○○
    Z-drugs
    70% ●○○

    Harm Reduction

    drugs.wiki

    Halazepam is an oral benzodiazepine that is converted hepatically to the long-acting active metabolite desmethyldiazepam (a.k.a. nordazepam), which has a very long and variable elimination half-life; this can cause next-day psychomotor impairment and cumulative sedation over repeated doses. To reduce stacking and accidental overdose, avoid same-day redosing and be especially cautious on consecutive days of use. Combining halazepam with other central nervous system depressants (alcohol, opioids, GHB/GBL, Z-drugs, barbiturates) markedly increases the risk of profound sedation, respiratory depression, aspiration, and death; such combinations should be avoided. Older adults and people with liver impairment are at higher risk for prolonged sedation, confusion, and falls; smaller test doses and longer spacing between doses reduce risk. Do not abruptly stop after days to weeks of daily or near-daily use; benzodiazepine withdrawal can include anxiety rebound, insomnia, tremor, and in severe cases seizures; gradual tapering is safer than sudden cessation. Driving and operating machinery should be avoided at least until the following day and longer if residual effects persist, as long-acting metabolites can impair reaction time and memory. In pregnancy and lactation, benzodiazepines and their long-acting metabolites can accumulate in the neonate and breastfed infant; if exposure occurs, monitor infants for sedation, poor feeding, and hypotonia. Snorting or injecting crushed tablets or powders provides no established benefit, increases harm, and may introduce insoluble binders; oral administration is the least risky ROA for pharmaceutical benzodiazepines. Use of CYP2C19 or CYP3A4 inhibitors (or poor-metabolizer genotypes) can increase desmethyldiazepam exposure by analogy with diazepam and clorazepate; consider this when other medications or grapefruit-like foods are involved.

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