Diclazepam

Last updated
Diclazepam
Diclazepam structure.svg
Diclazepam molecule ball.png
Clinical data
Routes of
administration
Oral, sublingual
Legal status
Legal status
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Elimination half-life ~42 hours [2]
Excretion Renal
Identifiers
  • 7-Chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C16H12Cl2N2O
Molar mass 319.19 g·mol−1
3D model (JSmol)
  • CN1C2=C(C=C(C=C2)Cl)C(C3=C(Cl)C=CC=C3)=NCC1=O
  • InChI=1S/C16H12Cl2N2O/c1-20-14-7-6-10(17)8-12(14)16(19-9-15(20)21)11-4-2-3-5-13(11)18/h2-8H,9H2,1H3
  • Key:VPAYQWRBBOGGPY-UHFFFAOYSA-N
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Diclazepam (Ro5-3448), also known as chlorodiazepam and 2'-chloro-diazepam, is a benzodiazepine and functional analog of diazepam. It was first synthesized by Leo Sternbach and his team at Hoffman-La Roche in 1960. [3] It is not currently approved for use as a medication, but rather sold as an unscheduled substance. [4] [5] [6] [7] Efficacy and safety have not been tested in humans.

Contents

In animal models, its effects are similar to diazepam, possessing long-acting anxiolytic, anticonvulsant, hypnotic, sedative, skeletal muscle relaxant, and amnestic properties.[ citation needed ]

Metabolism

Metabolism of this compound has been assessed, [2] revealing diclazepam has an approximate elimination half-life of 42 hours and undergoes N-demethylation to delorazepam, which can be detected in urine for 6 days following administration of the parent compound. [8] Other metabolites detected were lorazepam and lormetazepam which were detectable in urine for 19 and 11 days, respectively, indicating hydroxylation by cytochrome P450 enzymes occurring concurrently with N-demethylation.

United Kingdom

In the UK, diclazepam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other benzodiazepine drugs. [9]

United States

On December 23, 2022, the DEA announced it had begun consideration on the matter of placing Diclazepam under temporary Schedule I status. [10]

Later on July 25, 2023, the DEA published a pre-print notice that Diclazepam would become temporarily scheduled as a Schedule I controlled substance from 07/26/2023 to 07/26/2025. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine, specifically a cyclopyrrolone, used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do inducing sedation but not with the anti-anxiety properties of the benzodiazepines.

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

Fludiazepam, marketed under the brand name Erispan (エリスパン) is a potent benzodiazepine and 2ʹ-fluoro derivative of diazepam, originally developed by Hoffmann-La Roche in the 1960s. It is marketed in Japan and Taiwan. It exerts its pharmacological properties via enhancement of GABAergic inhibition. Fludiazepam has 4 times more binding affinity for benzodiazepine receptors than diazepam. It possesses anxiolytic, anticonvulsant, sedative, hypnotic and skeletal muscle relaxant properties. Fludiazepam has been used recreationally.

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

Etizolam is a thienodiazepine derivative which is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.

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

Phenazepam is a benzodiazepine drug, first developed in the Soviet Union in 1975, and now produced in Russia and several other countries.

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

Delorazepam, also known by the synonyms chlordesmethyldiazepam and nordiclazepam, is a drug which is a benzodiazepine and a derivative of desmethyldiazepam. It is marketed in Italy, where it is available under the trade name EN and Dadumir. Delorazepam (chlordesmethyldiazepam) is also an active metabolite of the benzodiazepine drugs diclazepam and cloxazolam. Adverse effects may include hangover type effects, drowsiness, behavioural impairments and short-term memory impairments. Similar to other benzodiazepines delorazepam has anxiolytic, skeletal muscle relaxant, hypnotic and anticonvulsant properties.

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

Meclonazepam ((S)-3-methylclonazepam) was discovered by a team at Hoffmann-La Roche in the 1970s and is a drug which is a benzodiazepine derivative similar in structure to clonazepam. It has sedative and anxiolytic actions like those of other benzodiazepines, and also has anti-parasitic effects against the parasitic worm Schistosoma mansoni.

<span class="mw-page-title-main">Ro5-4864</span> Chemical compound

Ro5-4864 (4'-chlorodiazepam) is a drug which is a benzodiazepine derivative of diazepam. However unlike most benzodiazepine derivatives, Ro5-4864 lacks affinity for GABAA receptors and lacks typical benzodiazepine effects, instead being sedative yet also convulsant and anxiogenic in effects. Ro5-4864 was found to be a potent ligand for the "peripheral benzodiazepine receptor", later renamed to mitochondrial translocator protein 18kDa (TSPO). Despite its convulsant effects, at lower doses Ro5-4864 has proved to be neuroprotective and has become widely used for research into the role of the TSPO protein in neurotoxicity. In vitro studies and rodent models also suggest the possibility of analgesic, antidepressant, cardioprotective, and anti-cancer effects.

<i>N</i>-Desalkylflurazepam Benzodiazepine analog

N-Desalkylflurazepam is a benzodiazepine analog and an active metabolite of several other benzodiazepine drugs including flurazepam, flutoprazepam, fludiazepam, midazolam, flutazolam, quazepam, and ethyl loflazepate. It is long-acting, prone to accumulation, and binds unselectively to the various benzodiazepine receptor subtypes. It has been sold as a designer drug from 2016 onward.

<span class="mw-page-title-main">U-47700</span> Opioid analgesic

U-47700, also known as U4, pink heroin, pinky, and pink, is an opioid analgesic drug developed by a team at Upjohn in the 1970s which has around 7.5 times the potency of morphine in animal models.

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

Pyrazolam (SH-I-04) is a benzodiazepine derivative originally developed by a team led by Leo Sternbach at Hoffman-La Roche in the 1970s. It has since been "rediscovered" and sold as a designer drug since 2012.

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

Flubromazepam is a benzodiazepine derivative which was first synthesized in 1960, but was never marketed and did not receive any further attention or study until late 2012 when it appeared on the grey market as a novel designer drug.

<span class="mw-page-title-main">3-Hydroxyphenazepam</span> Benzodiazepine medication

3-Hydroxyphenazepam is a benzodiazepine with hypnotic, sedative, anxiolytic, and anticonvulsant properties. It is an active metabolite of phenazepam, as well as the active metabolite of the benzodiazepine prodrug cinazepam. Relative to phenazepam, 3-hydroxyphenazepam has diminished myorelaxant properties, but is about equivalent in most other regards. 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. It has been sold as a designer drug.

<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

Flubromazolam (JYI-73) is a triazolobenzodiazepine (TBZD), which are benzodiazepine (BZD) derivatives. Flubromazolam is reputed to be highly potent, and concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg. Life-threatening adverse reactions have been observed at doses of only 3 mg of flubromazolam.

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

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

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

Flualprazolam is a tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It was first synthesised in 1976, but was never marketed. It can be seen as the triazolo version of fludiazepam. It has subsequently been sold as a designer drug, first being definitively identified as such in Sweden in 2018. It can be described as the 2'-fluoro derivative of alprazolam or the fluoro instead of chloro analogue of triazolam, and has similar sedative and anxiolytic effects.

<span class="mw-page-title-main">5F-MDMB-PICA</span> Chemical compound

5F-MDMB-PICA (MDMB-5F-PICA) is a designer drug and synthetic cannabinoid. In 2018, it was the fifth-most common synthetic cannabinoid identified in drugs seized by the Drug Enforcement Administration.

<span class="mw-page-title-main">4'-Chlorodeschloroalprazolam</span> Chemical compound

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References

  1. Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. 1 2 Moosmann B, Bisel P, Auwärter V (July–August 2014). "Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics". Drug Testing and Analysis. 6 (7–8): 757–763. doi:10.1002/dta.1628. PMID   24604775.
  3. US 3136815,"Amino substituted benzophenone oximes and derivatives thereof"
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  5. Høiseth G, Tuv SS, Karinen R (November 2016). "Blood concentrations of new designer benzodiazepines in forensic cases". Forensic Science International. 268: 35–38. doi:10.1016/j.forsciint.2016.09.006. PMID   27685473.
  6. 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.
  7. Manchester KR, Waters L, Haider S, Maskell PD (July 2022). "The blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepines". Forensic Toxicology. 40 (2): 349–356. doi: 10.1007/s11419-022-00616-y . PMC   9715504 . PMID   36454409. S2CID   247455284.
  8. Bareggi SR, Truci G, Leva S, Zecca L, Pirola R, Smirne S (1988). "Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans". European Journal of Clinical Pharmacology. 34 (1): 109–112. doi:10.1007/bf01061430. PMID   2896126. S2CID   1574555.
  9. "The Misuse of Drugs Act 1971 (Amendment) Order 2017".
  10. "(Proposed Rule) Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule I". Federal Register . DEA. December 23, 2022.
  11. "Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule I" (PDF). Federal Register . DEA. July 25, 2023. Retrieved 2023-07-25.