MT-45

Last updated

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
  • 1-Cyclohexyl-4-(1,2-diphenylethyl)piperazine
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C24H32N2
Molar mass 348.534 g·mol−1
3D model (JSmol)
  • c3ccccc3CC(c2ccccc2)N(CC1)CCN1C4CCCCC4
  • InChI=1S/C24H32N2/c1-4-10-21(11-5-1)20-24(22-12-6-2-7-13-22)26-18-16-25(17-19-26)23-14-8-3-9-15-23/h1-2,4-7,10-13,23-24H,3,8-9,14-20H2 X mark.svgN
  • Key:IGBRRSIHEGCUEN-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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]

Contents

2F-MT-45. 2F-MT-45 structure.png
2F-MT-45.

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 The cause for this is unclear, although a structural similarity to a withdrawn drug triparanol which caused similar side effects has been noted.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

Related Research Articles

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

Lefetamine (Santenol) is a drug which is a stimulant and also an analgesic with effects comparable to codeine.

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

Ohmefentanyl is an extremely potent opioid analgesic drug which selectively binds to the μ-opioid receptor.

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

Dezocine, sold under the brand name Dalgan, is an atypical opioid analgesic which is used in the treatment of pain. It is used by intravenous infusion and intramuscular injection.

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

Metazocine is an opioid analgesic related to pentazocine. While metazocine has significant analgesic effects, mediated through a mixed agonist–antagonist action at the mu opioid receptor, its clinical use is limited by dysphoric and hallucinogenic effects which are most likely caused by activity at kappa opioid receptors and/or sigma receptors.

<span class="mw-page-title-main">BW373U86</span> Opioid analgesic drug used in research

(+)-BW373U86 is an opioid analgesic drug used in scientific research.

<span class="mw-page-title-main">14-Methoxymetopon</span> Chemical compound

14-Methoxymetopon is an experimental opioid drug developed by a team led by Professor Helmut Schmidhammer at the University of Innsbruck in the mid-1990s. It is a derivative of metopon in which a methoxy group has been inserted at the 14-position. It is a highly potent analgesic drug that is around 500 times stronger than morphine when administered systemically; however, when given spinally or supraspinally, it exhibits analgesic activity up to a million fold greater than morphine. It binds strongly to the μ-opioid receptor and activates it to a greater extent than most similar opioid drugs. This produces an unusual pharmacological profile, and although 14-methoxymetopon acts as a potent μ-opioid full agonist in regard to some effects such as analgesia, a ceiling effect is seen on other effects such as constipation and respiratory depression which is believed to involve interaction with the κ-opioid receptor

<span class="mw-page-title-main">Azaprocin</span> Opioid analgesic drug

Azaprocin is a drug which is an opioid analgesic with approximately ten times the potency of morphine, and a fast onset and short duration of action. It was discovered in 1963, but has never been marketed.

<span class="mw-page-title-main">Alazocine</span> Synthetic opioid analgesic

Alazocine, also known more commonly as N-allylnormetazocine (NANM), is a synthetic opioid analgesic of the benzomorphan family related to metazocine, which was never marketed. In addition to its opioid activity, the drug is a sigma receptor agonist, and has been used widely in scientific research in studies of this receptor. Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist. Moreover, one of its enantiomers was the first compound that was found to selectively label the σ1 receptor, and led to the discovery and characterization of the receptor.

<span class="mw-page-title-main">Arylcyclohexylamine</span> Class of chemical compounds

Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.

<span class="mw-page-title-main">Tiospirone</span> Atypical antipsychotic drug

Tiospirone (BMY-13,859), also sometimes called tiaspirone or tiosperone, is an atypical antipsychotic of the azapirone class. It was investigated as a treatment for schizophrenia in the late 1980s and was found to have an effectiveness equivalent to those of typical antipsychotics in clinical trials but without causing extrapyramidal side effects. However, development was halted and it was not marketed. Perospirone, another azapirone derivative with antipsychotic properties, was synthesized and assayed several years after tiospirone. It was found to be both more potent and more selective in comparison and was commercialized instead.

<span class="mw-page-title-main">Osemozotan</span> Pharmaceutical drug

Osemozotan (MKC-242) is a selective 5-HT1A receptor agonist with some functional selectivity, acting as a full agonist at presynaptic and a partial agonist at postsynaptic 5-HT1A receptors. 5-HT1A receptor stimulation influences the release of various neurotransmitters including serotonin, dopamine, norepinephrine, and acetylcholine. 5-HT1A receptors are inhibitory G protein-coupled receptor.

<span class="mw-page-title-main">GR-89696</span> Chemical compound

GR-89696 is a drug which acts as a highly selective κ-opioid agonist. It has been studied in various animal species, and has been described as selective for the κ2 subtype. Recent studies have suggested that GR-89696 and related κ2-selective agonists may be useful for preventing the itching which is a common side effect of conventional opioid analgesic drugs, without the additional side effects of non-selective kappa agonists. The structure bound to the κ-opioid receptor has been reported.

<span class="mw-page-title-main">AD-1211</span> Opioid analgesic drug

AD-1211 is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-prenyl-piperazine derivative, which is structurally unrelated to most other opioid drugs. The (S)-enantiomers in this series are more active as opioid agonists, but the less active (R)-enantiomer of this compound, AD-1211, is a mixed agonist–antagonist at opioid receptors with a similar pharmacological profile to pentazocine, and has atypical opioid effects with little development of tolerance or dependence seen after extended administration in animal studies.

<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">RB-64</span> Chemical compound

RB-64 is a semi-synthetic derivative of salvinorin A. It is an irreversible agonist, with a reactive thiocyanate group that forms a bond to the κ-opioid receptor (KOR), resulting in very high potency. It is functionally selective, activating G proteins more potently than β-arrestin-2. RB-64 has a bias factor of up to 96 and is analgesic with fewer of the side-effects associated with unbiased KOR agonists. The analgesia is long-lasting. Compared with unbiased agonists, RB-64 evokes considerably less receptor internalization.

<span class="mw-page-title-main">Ephenidine</span> Dissociative anesthetic designer drug

Ephenidine is a dissociative anesthetic that has been sold online as a designer drug. It is illegal in some countries as a structural isomer of the banned opioid drug lefetamine, but has been sold in countries where it is not yet banned.

<span class="mw-page-title-main">Bucinnazine</span> Opioid analgesic drug

Bucinnazine is an opioid analgesic drug that was widely used in China to treat pain in cancer patients as of 1986. It is one of the most potent compounds among a series of piperazine-amides first synthesized and reported in Japan in the 1970s. Bucinnazine has analgesic potency comparable to that of morphine but with a relatively higher therapeutic index.

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

Diphenpipenol is an opioid analgesic drug invented in the 1970s by Dainippon Pharmaceutical Co. It is chemically a 1-substituted-4-(1,2-diphenylethyl)piperazine derivative related to compounds such as MT-45 and AD-1211, but diphenpipenol is the most potent compound in the series, with the more active (S) enantiomer being around 105 times the potency of morphine in animal studies. This makes it a similar strength to fentanyl and its analogues, and consequently diphenpipenol can be expected to pose a significant risk of producing life-threatening respiratory depression, as well as other typical opioid side effects such as sedation, itching, nausea and vomiting.

<span class="mw-page-title-main">HS665</span> Chemical compound

HS665 is a drug which acts as a potent and selective κ-opioid receptor agonist, and has analgesic effects in animal studies. HS665 is not an agonist for the mu receptor, leading to less potential for abuse.

References

  1. USpatent 3957788,Haruki Nishimura, Hitoshi Uno, Kagayaki Natsuka, Noriaki Shimokawa, Masanao Shimizu, Hideo Nakamura,"1-Substituted-4-(1,2-diphenylethyl)piperazine derivatives and their salts",published 1975-15-01,issued 1976-18-05
  2. Natsuka K, Nakamura H, Uno H, Umemoto S (December 1975). "Studies on 1-substituted 4-(1,2-diphenylethyl)piperazine derivatives and their analgesic activities. 1". Journal of Medicinal Chemistry. 18 (12): 1240–4. doi:10.1021/jm00246a014. PMID   1195277.
  3. Nakamura H, Shimizu M (May 1976). "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. PMID   962421.
  4. US Patent 4080453
  5. Natsuka K, Nakamura H, Negoro T, Uno H, Nishimura H (December 1978). "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. doi:10.1021/jm00210a017. PMID   722735.
  6. Shimokawa N, Nakamura H, Shimakawa K, Minami H, Nishimura H (January 1979). "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. doi:10.1021/jm00187a014. PMID   106119.
  7. Nakamura H, Ishii D, Yokoyama Y, Motoyoshi S, Natsuka K, Shimizu M (September 1980). "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. doi:10.1111/j.2042-7158.1980.tb13020.x. PMID   6107365. S2CID   27764413.
  8. Nozaki M, Niwa M, Imai E, Hori M, Fujimura H (1983). "(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. doi:10.1016/0024-3205(83)90534-9. PMID   6319898.
  9. Natsuka K, Nakamura H, Nishikawa Y, Negoro T, Uno H, Nishimura H (October 1987). "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. doi:10.1021/jm00393a017. PMID   3656354.
  10. Natsuka K, Nishikawa Y, Nakamura H (December 1999). "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. doi: 10.1248/cpb.47.1790 . PMID   10748722.
  11. Baptista-Hon DT, Smith M, Singleton S, Antonides LH, Nic Daeid N, McKenzie C, Hales TG (August 2020). "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. doi: 10.1111/bph.15064 . PMC   7348096 . PMID   32246840.
  12. Helander A, Bäckberg M, Beck O (2014). "MT-45, a new psychoactive substance associated with hearing loss and unconsciousness". Clinical Toxicology. 52 (8): 901–4. doi:10.3109/15563650.2014.943908. PMID   25175898. S2CID   37311206.
  13. Helander A, Bradley M, Hasselblad A, Norlén L, Vassilaki I, Bäckberg M, Lapins J (April 2017). "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. doi:10.1111/bjd.15174. PMID   27976363. S2CID   39249889.
  14. Wallach JV, Morris H, Brandt SD (August 2017). "Is nitrogen mustard contamination responsible for the reported MT-45 toxicity?" (PDF). The British Journal of Dermatology. 177 (2): 594–595. doi:10.1111/bjd.15507. PMID   28369837. S2CID   30128050.
  15. Helander A, Bradley M, Lapins J (August 2017). "'Is nitrogen mustard contamination responsible for the reported MT-45 toxicity?' Reply from the authors". The British Journal of Dermatology. 177 (2): 595. doi:10.1111/bjd.15676. PMID   28626874. S2CID   26911685.
  16. Solimini R, Pichini S, Pacifici R, Busardò FP, Giorgetti R (2018). "Pharmacotoxicology of Non-fentanyl Derived New Synthetic Opioids". Frontiers in Pharmacology. 9: 654. doi: 10.3389/fphar.2018.00654 . PMC   6020781 . PMID   29973882.
  17. McKenzie C, Sutcliffe OB, Read KD, Scullion P, Epemolu O, Fletcher D, et al. (2018). "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. doi:10.1007/s11419-018-0413-1. PMC   6002428 . 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. Retrieved 11 March 2015.
  19. "Látky, o které byl doplněn seznam č. 4 psychotropních látek (příloha č. 4 k nařízení vlády č. 463/2013 Sb.)" (PDF) (in Czech). Ministerstvo zdravotnictví. Archived from the original (PDF) on 2016-03-09. Retrieved 2016-02-06.
  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".