Meclonazepam

Meclonazepam

Clinical data
ATC code	none
Legal status
Legal status	CA: Schedule IV DE: NpSG (Industrial and scientific use only) UK:Under Psychoactive Substances Act
Identifiers
IUPAC name (3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
CAS Number	58662-84-3  N
PubChem CID	3033985
ChemSpider	2298544  Y
UNII	RN43209SMA
ChEMBL	ChEMBL351821  N
CompTox Dashboard (EPA)	DTXSID10207366
Chemical and physical data
Formula	C16H12ClN3O3
Molar mass	329.74 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=N(C1=CC2=C(NC([C@H](C)N=C2C3=CC=CC=C3)=O)C=C1)=O
InChI InChI=1S/C16H12ClN3O3/c1-9-16(21)19-14-7-6-10(20(22)23)8-12(14)15(18-9)11-4-2-3-5-13(11)17/h2-9H,1H3,(H,19,21)/t9-/m0/s1 Y Key:LMUVYJCAFWGNSY-VIFPVBQESA-N Y
NY  (what is this?)    (verify)

Meclonazepam ^[1] ((S)-3-methylclonazepam) is a benzodiazepine derivative similar in structure to clonazepam. It was first discovered by a team at Hoffmann-La Roche in the 1970s. ^[2] It has sedative and anxiolytic actions like those of other benzodiazepines, ^[3] and also has anti-parasitic effects against the parasitic worm Schistosoma mansoni . ^[4]

Meclonazepam was never used as medicine and instead appeared online as a designer drug. ^{[5] [6] [7] [8]}

Pharmacology

Its sedative and anxiolytic abilities are attributed to the same mechanism used by other benzodiazepine drugs: modulation of the GABA_A receptor in the brain. This psychoactive activity makes it useful for recreational use. ^[7] The sedating side effect would also make it unsuitable for routine use as an antiparasitical. ^[9]

Schistosomal parasites do not have an ortholog of the GABA_A receptor. Instead, meclonazepam seems to cause a rapid calcium influx, leading to muscle contraction and tegument damage. In 2023, meclonazepam is shown to activate a calcium-permeable schistosome TRP (transient receptor potential), making this TRP a very likely candidate for its parasite receptor. ^[9]

Some work has been done to produce two meclonazepam derivatives that show less sedation and more anti-parasite activity in mice. They seem to do this by crossing the blood-brain barrier less readily. ^[9]

Legal Issues

United Kingdom

In the UK, meclonazepam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs. ^[10]

See also

• 3-Hydroxyphenazepam
• Desmethylflunitrazepam
• Nifoxipam
• Oxazepam
• Phenazepam
• Ro05-4082
• SH-I-048A

References

1. US 4031078,Szente A,"Benzodiazepine derivatives",issued 21 June 1977, assigned to Hoffmann La Roche Inc. 
2. The Lundbeck Institute. "Meclonazepam". Psychotropics. Lundbeck.
3. Ansseau M, Doumont A, Thiry D, von Frenckell R, Collard J (1985). "Initial study of methylclonazepam in generalized anxiety disorder. Evidence for greater power in the cross-over design" (PDF). Psychopharmacology. 87 (2): 130–135. doi:10.1007/bf00431795. hdl:2268/259489. PMID   3931136. S2CID   9776700.
4. O'Boyle C, Lambe R, Darragh A (1985). "Central effects in man of the novel schistosomicidal benzodiazepine meclonazepam". European Journal of Clinical Pharmacology. 29 (1): 105–108. doi:10.1007/bf00547377. PMID   4054198. S2CID   1150292.
5. Meyer MR, Bergstrand MP, Helander A, Beck O (May 2016). "Identification of main human urinary metabolites of the designer nitrobenzodiazepines clonazolam, meclonazepam, and nifoxipam by nano-liquid chromatography-high-resolution mass spectrometry for drug testing purposes". Analytical and Bioanalytical Chemistry. 408 (13): 3571–3591. doi:10.1007/s00216-016-9439-6. PMID   27071765. S2CID   25831532.
6. 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.
7. 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.
8. 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.
9. Mian MY, Sharmin D, Mondal P, Belayet JB, Hossain MM, McCusker P, et al. (September 2024). "Development of non-sedating benzodiazepines with in vivo antischistosomal activity". Antimicrobial Agents and Chemotherapy. 68 (9) e00369-24: e0036924. doi:10.1128/aac.00369-24. PMC   11373208 . PMID   39136467.
10. "The Misuse of Drugs Act 1971 (Amendment) Order 2017".

Further reading

• Abdul-Ghani RA, Loutfy N, Hassan A (October 2009). "Experimentally promising antischistosomal drugs: a review of some drug candidates not reaching the clinical use". Parasitology Research. 105 (4): 899–906. doi:10.1007/s00436-009-1546-2. PMID   19588166. S2CID   24122988.