Chemistry:MT-45

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Short description: Chemical compound
MT-45
MT-45 svg.svg
Clinical data
Other namesMT-45, IC-6
Routes of
administration		oral administration rectal administration
ATC code
  • None
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC24H32N2
Molar mass348.534 g·mol−1
3D model (JSmol)
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MT-45 (IC-6) is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co.[1] It is chemically a 1-substituted-4-(1,2-diphenylethyl) piperazine derivative, which is structurally unrelated to most other opioid drugs. Racemic MT-45 has around 80% the potency of morphine, with almost all opioid activity residing in the (S) enantiomer (the opposite stereochemistry from the related drug lefetamine).[2][3] It has been used as a lead compound from which a large family of potent opioid drugs[4] have been developed, including full agonists, partial agonists, and antagonists at the three main opioid receptor subtypes.[5][6][7][8][9][10] Fluorinated derivatives of MT-45 such as 2F-MT-45 are significantly more potent as μ-opioid receptor agonists, and one of its main metabolites 1,2-diphenylethylpiperazine also blocks NMDA receptors.[11]

2F-MT-45. [1]

Side effects

Recreational use of MT-45 has been associated with unconsciousness and overdose, as well as a range of unusual side effects not typically seen with other opioid agonists, including hearing loss, hair depigmentation, alopecia, cataracts, and skin and nail reactions such as dermatitis and Mees lines. The cause for this is unclear, although a structural similarity to a withdrawn drug triparanol which caused similar side effects has been noted.[12][13][14][15][16][17]

Legality

MT-45 became a class A drug in the UK on 11 March 2015.[18]

MT-45 is banned in the Czech Republic.[19]

The Canadian Controlled Drugs and Substances Act was amended in 2016 to include the substance as a Schedule I substance. Possession without legal authority can result in maximum 7 years imprisonment. Further, Health Canada amended the Food and Drug Regulations in May 2016 to classify MT-45 as a restricted drug.[20] Only those with a law enforcement agency, person with an exemption permit or institutions with Minister's authorization may possess the drug in Canada.

In the United States, the DEA placed MT-45 in Schedule 1 of the Controlled Substance Act. This took effect on January 12, 2018.[21]

See also

References

  1. ↑ Haruki Nishimura, Hitoshi Uno, Kagayaki Natsuka, Noriaki Shimokawa, Masanao Shimizu, Hideo Nakamura, "1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives and their salts", US patent 3957788, published 1975-15-01, issued 1976-18-05
  2. ↑ "Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1". Journal of Medicinal Chemistry 18 (12): 1240–4. December 1975. doi:10.1021/jm00246a014. PMID 1195277. 
  3. ↑ "Comparative study of 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine and its enantiomorphs on analgesic and other pharmacological activities in experimental animals". Archives Internationales de Pharmacodynamie et de Thérapie 221 (1): 105–21. May 1976. PMID 962421. 
  4. ↑ US Patent 4080453
  5. ↑ "Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 2. Structure-activity relationships of 1-cycloalkyl-4-(1,2-diphenylethyl)piperazines". Journal of Medicinal Chemistry 21 (12): 1265–9. December 1978. doi:10.1021/jm00210a017. PMID 722735. 
  6. ↑ "Studies on analgesic agents. 1.1a Preparation of 1,2-diphenyl-2-(4-substituted 1-piperazinyl)ethanol derivatives and structure-activity relationships". Journal of Medicinal Chemistry 22 (1): 58–63. January 1979. doi:10.1021/jm00187a014. PMID 106119. 
  7. ↑ "Analgesic and other pharmacological activities of a new narcotic antagonist analgesic (−)-1-(3-methyl-2-butenyl)-4-[2-(3-hydroxyphenyl)-1-phenylethyl]-piperazine and its enantiomorph in experimental animals". The Journal of Pharmacy and Pharmacology 32 (9): 635–42. September 1980. doi:10.1111/j.2042-7158.1980.tb13020.x. PMID 6107365. 
  8. ↑ "(1,2-Diphenylethyl) piperazines as potent opiate-like analgesics; the unusual relationships between stereoselectivity and affinity to opioid receptor". Life Sciences 33 (Suppl 1): 431–4. 1983. doi:10.1016/0024-3205(83)90534-9. PMID 6319898. 
  9. ↑ "Synthesis and structure-activity relationships of 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives having narcotic agonist and antagonist activity". Journal of Medicinal Chemistry 30 (10): 1779–87. October 1987. doi:10.1021/jm00393a017. PMID 3656354. 
  10. ↑ "Roles of two basic nitrogen atoms in 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives in production of opioid agonist and antagonist activities". Chemical & Pharmaceutical Bulletin 47 (12): 1790–3. December 1999. doi:10.1248/cpb.47.1790. PMID 10748722. 
  11. ↑ "Activation of μ-opioid receptors by MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) and its fluorinated derivatives". British Journal of Pharmacology 177 (15): 3436–48. August 2020. doi:10.1111/bph.15064. PMID 32246840. 
  12. ↑ "MT-45, a new psychoactive substance associated with hearing loss and unconsciousness". Clinical Toxicology 52 (8): 901–4. 2014. doi:10.3109/15563650.2014.943908. PMID 25175898. 
  13. ↑ "Acute skin and hair symptoms followed by severe, delayed eye complications in subjects using the synthetic opioid MT-45". The British Journal of Dermatology 176 (4): 1021–1027. April 2017. doi:10.1111/bjd.15174. PMID 27976363. 
  14. ↑ "Is nitrogen mustard contamination responsible for the reported MT-45 toxicity?". The British Journal of Dermatology 177 (2): 594–595. August 2017. doi:10.1111/bjd.15507. PMID 28369837. http://researchonline.ljmu.ac.uk/id/eprint/6079/1/BJD_Commentary_BJD-2017-0053_accepted_uncorrected.pdf. 
  15. ↑ "'Is nitrogen mustard contamination responsible for the reported MT-45 toxicity?' Reply from the authors". The British Journal of Dermatology 177 (2): 595. August 2017. doi:10.1111/bjd.15676. PMID 28626874. 
  16. ↑ "Pharmacotoxicology of Non-fentanyl Derived New Synthetic Opioids". Frontiers in Pharmacology 9: 654. 2018. doi:10.3389/fphar.2018.00654. PMID 29973882. 
  17. ↑ "Chemical synthesis, characterisation and in vitro and in vivo metabolism of the synthetic opioid MT-45 and its newly identified fluorinated analogue 2F-MT-45 with metabolite confirmation in urine samples from known drug users". Forensic Toxicology 36 (2): 359–374. 2018. doi:10.1007/s11419-018-0413-1. PMID 29963206. 
  18. ↑ "Circular 003/2015: a change to the Misuse of Drugs Act 1971: control of MT-45 and 4,4'-DMAR". UK Home Office. 20 February 2015. https://www.gov.uk/government/publications/circular-0032015-a-change-to-the-misuse-of-drugs-act-1971-control-of-mt-45-and-44-dmar. 
  19. ↑ "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" (in cs). Ministerstvo zdravotnictví. http://www.mzcr.cz/Admin/_upload/files/3/Nov%C3%A9%20PL.pdf. 
  20. ↑ Regulations Amending the Food and Drug Regulations (Parts G and J — Lefetamine, AH-7921, MT-45 and W-18)
  21. ↑ "2017 - Final Order: Placement of MT-45 into Schedule I". https://www.deadiversion.usdoj.gov/fed_regs/rules/2017/fr1213_3.htm. 



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