Meclonazepam

Meclonazepam
Clinical data
ATC code
  • none
Legal status
Legal status
Identifiers
  • (3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC16H12ClN3O3
Molar mass329.74 g·mol−1
3D model (JSmol)
  • O=N(C1=CC2=C(NC([C@H](C)N=C2C3=CC=CC=C3)=O)C=C1)=O
  • 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 checkY
  • Key:LMUVYJCAFWGNSY-VIFPVBQESA-N checkY
 ☒NcheckY (what is this?)  (verify)

Meclonazepam[1] ((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.[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

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Its sedative and anxiolytic abilities are attributed to the same mechanism used by other benzodiazepine drugs: modulation of the GABAA 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 GABAA 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]

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United Kingdom

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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

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References

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  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. 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. ^ a b 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.
  8. ^ 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.
  9. ^ a b c 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): e0036924. doi:10.1128/aac.00369-24. PMID 39136467.
  10. ^ "The Misuse of Drugs Act 1971 (Amendment) Order 2017".

Further reading

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  • 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.
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