Diclazepam

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.

Diclazepam

Clinical data
Routes of administration	Oral, sublingual
Legal status
Legal status	BR: Class B1 (Psychoactive drugs)^[1] CA: Schedule IV DE: Anlage II (Authorized trade only, not prescriptible) UK: Class C US: Schedule I
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Elimination half-life	~42 hours^[2]
Excretion	Renal
Identifiers
IUPAC name 7-Chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
CAS Number	2894-68-0^Y
PubChem CID	76168
ChemSpider	68652
UNII	070818R7PB
KEGG	C22813^Y
CompTox Dashboard (EPA)	DTXSID30183138
Chemical and physical data
Formula	C16H12Cl2N2O
Molar mass	319.19 g·mol^−1
3D model (JSmol)	Interactive image
SMILES CN1C2=C(C=C(C=C2)Cl)C(C3=C(Cl)C=CC=C3)=NCC1=O
InChI 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
^NY (what is this?)  (verify)

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.

Legal status

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

• Diazepam
• Difludiazepam
• Delorazepam (Nordiclazepam)
• Lorazepam
• Phenazepam
• Ro09-9212
• Ro5-4864 (4'-Chlorodiazepam)
• Ro07-5220 (6'-Chlorodiclazepam)

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). from the original on 2023-08-03. Retrieved 2023-08-16.
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" 
4. 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.
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 D_7.4 , pK_a 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 GABA_A-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.