3-Hydroxyphenazepam

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3-Hydroxyphenazepam
3-Hydroxyphenazepam.svg
3-Hydroxyphenazepam ball-and-stick model.png
Clinical data
ATC code
  • None
Legal status
Legal status
Identifiers
  • 7-Bromo-5-(2-chlorophenyl)-3-hydroxy-1,3-dihydro-2H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H10BrClN2O2
Molar mass 365.61 g·mol−1
3D model (JSmol)
  • c1ccc(c(c1)C2=NC(C(=O)Nc3c2cc(cc3)Br)O)Cl
  • InChI=1S/C15H10BrClN2O2/c16-8-5-6-12-10(7-8)13(19-15(21)14(20)18-12)9-3-1-2-4-11(9)17/h1-7,15,21H,(H,18,20)
  • Key:KRJKJUWAZOWXNV-UHFFFAOYSA-N

3-Hydroxyphenazepam is a benzodiazepine with hypnotic, sedative, anxiolytic, and anticonvulsant properties. [1] It is an active metabolite of phenazepam, [1] [2] as well as the active metabolite of the benzodiazepine prodrug cinazepam. [3] Relative to phenazepam, 3-hydroxyphenazepam has diminished myorelaxant properties, but is about equivalent in most other regards. [1] Like other benzodiazepines, 3-hydroxyphenazepam behaves as a positive allosteric modulator of the benzodiazepine site of the GABAA receptor with an EC50 value of 10.3 nM. [4] [5] [6] It has been sold as a designer drug. [7] [8] [9] [10]

See also

Related Research Articles

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<span class="mw-page-title-main">Ethyl loflazepate</span> Chemical compound

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<span class="mw-page-title-main">Phenazepam</span> Benzodiazepine drug

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<span class="mw-page-title-main">Meclonazepam</span> Chemical compound

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<span class="mw-page-title-main">Pyrazolam</span> Benzodiazepine

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<span class="mw-page-title-main">Diclazepam</span> Benzodiazepine medication

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<span class="mw-page-title-main">Cinazepam</span> Benzodiazepine medication

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<span class="mw-page-title-main">Clonazolam</span> Benzodiazepine

Clonazolam is a drug of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. Although little research has been done about its effects and metabolism, it is sold online as a designer drug.

<span class="mw-page-title-main">Flubromazolam</span> Triazolobenzodiazepine drug

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<span class="mw-page-title-main">Ephenidine</span> Dissociative anesthetic designer drug

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<span class="mw-page-title-main">Deschloroetizolam</span> Chemical compound

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<span class="mw-page-title-main">Nifoxipam</span> Benzodiazepine designer drug

Nifoxipam is a benzodiazepine that is a minor metabolite of flunitrazepam and has been sold online as a designer drug.

<span class="mw-page-title-main">Metizolam</span> Chemical compound

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<span class="mw-page-title-main">Desmethylflunitrazepam</span> Chemical compound

Desmethylflunitrazepam (also known as norflunitrazepam, Ro05-4435 and fonazepam) is a benzodiazepine that is a metabolite of flunitrazepam and has been sold online as a designer drug. It has an IC50 value of 1.499 nM for the GABAA receptor.

<span class="mw-page-title-main">Nitrazolam</span> Benzodiazepine designer drug

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<span class="mw-page-title-main">Flunitrazolam</span> Triazolobenzodiazepine drug

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<span class="mw-page-title-main">Cloniprazepam</span> Benzodiazepine drug

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References

  1. 1 2 3 Valdman AV, ed. (31 May 1986). Drug dependence and emotional behavior: neurophysiological and neurochemical approaches. Consultants Bureau. ISBN   978-0-306-10984-3.
  2. Komsta L, Waksmundzka-Hajnos M, Sherma J, eds. (20 December 2013). Thin Layer Chromatography in Drug Analysis. CRC Press. pp. 299–. ISBN   978-1-4665-0715-9.
  3. Schukin SI, Zinkovsky VG, Zhuk OV (2011). "Elimination kinetics of the novel prodrug cinazepam possessing psychotropic activity in mice". Pharmacological Reports. 63 (5): 1093–1100. doi:10.1016/s1734-1140(11)70628-4. PMID   22180351. S2CID   4744087.
  4. "Phenazepam Pre-Review Report" (PDF). World Health Organization (WHO). November 2015.
  5. Kopanitsa MV, Zbarska SM, Boychuk YA, Krishtal OA (2000). "Modulation of GABA-activated currents by phenazepam and its metabolites in isolated rat purkinje neurons". Neurophysiology. 32 (3): 192. doi:10.1007/BF02506568. ISSN   0090-2977. S2CID   32313668.
  6. Golovenko NY, Larionov VB (2014). "Pharmacodynamical and Neuroreceptor Analysis of the Permeability of the Blood-Brain Barrier for Derivatives of 1,4-Benzodiazepine". Neurophysiology. 46 (3): 199–205. doi:10.1007/s11062-014-9429-2. ISSN   0090-2977. S2CID   33732669.
  7. "3-hydroxyphenazepam". New Synthetic Drugs Database. Archived from the original on 2016-09-28. Retrieved 2016-05-30.
  8. Pettersson Bergstrand M, Helander A, Hansson T, Beck O (April 2017). "Detectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assays". Drug Testing and Analysis. 9 (4): 640–645. doi:10.1002/dta.2003. PMID   27366870.
  9. Moosmann B, Bisel P, Franz F, Huppertz LM, Auwärter V (November 2016). "Characterization and in vitro phase I microsomal metabolism of designer benzodiazepines - an update comprising adinazolam, cloniprazepam, fonazepam, 3-hydroxyphenazepam, metizolam and nitrazolam". Journal of Mass Spectrometry. 51 (11): 1080–1089. Bibcode:2016JMSp...51.1080M. doi:10.1002/jms.3840. PMID   27535017.
  10. Manchester KR, Maskell PD, Waters L (March 2018). "Experimental versus theoretical log D7.4 , pKa and plasma protein binding values for benzodiazepines appearing as new psychoactive substances". Drug Testing and Analysis. 10 (8): 1258–1269. doi:10.1002/dta.2387. PMID   29582576. S2CID   31098917.