Methiopropamine

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Methiopropamine
Methiopropamine-2d-skeletal.svg
Systematic (IUPAC) name
1-(thiophen-2-yl)-2-methylaminopropane
Clinical data
Legal status
  • US: Unscheduled - Possible Schedule II Analog
Identifiers
CAS number801156-47-8 N
7464-94-0 (hydrochloride)
ATC codeN06AA
PubChemCID 436156
ChemSpider385727 YesY
Chemical data
FormulaC8H13NS 
Mol. mass155.261 g/mol
 N (what is this?)  (verify)
 
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Methiopropamine
Methiopropamine-2d-skeletal.svg
Systematic (IUPAC) name
1-(thiophen-2-yl)-2-methylaminopropane
Clinical data
Legal status
  • US: Unscheduled - Possible Schedule II Analog
Identifiers
CAS number801156-47-8 N
7464-94-0 (hydrochloride)
ATC codeN06AA
PubChemCID 436156
ChemSpider385727 YesY
Chemical data
FormulaC8H13NS 
Mol. mass155.261 g/mol
 N (what is this?)  (verify)

Methiopropamine (MPA) is a thiophene ring-based structural analog of methamphetamine originally reported in 1942.[1] Chemically it is not a phenethylamine or amphetamine and is not their functional analog either. It originally appeared for public sale in the UK in December 2010 as a "research chemical" or "legal high", recently branded as Blow.[2] It has limited popularity as a recreational stimulant.[3][unreliable source?]

Pharmacology[edit]

Methiopropamine functions as a selective norepinephrine-dopamine reuptake inhibitor that is approximately 1.85 times more selective for norepinephrine than dopamine. It is approximately one third as potent as dextroamphetamine as a norepinephrine reuptake inhibitor and one fifth as much as a dopamine reuptake inhibitor. It displays negligible activity as a serotonin reuptake inhibitor.[4]

Metabolism[edit]

Methiopropamine metabolism is somewhat similar to methamphetamine. Hydroxylation, demethylation and deamination are in common. Formation of thiophene S-oxide is different, as is the end product which will probably be (substituted) thiophene-2-carboxylic acid. It is then excreted in urine. Compounds on red are inactive.

For N-alkyl amphetamines deamination and N-dealkylation are the major elimination pathways and renal excretion is a minor one.[5] Methiopropamine is metabolized into active thiopropamine, 4-hydroxymethiopropamine and thiophene S-oxides.[6][7] These N-demethylated metabolites are further deaminated by the cytochrome P450 enzyme CYP2C19 in the liver transforming them into inactive 1-(thiophen-2-yl)-2-propan-2-one which can be seen as a phenylacetone derivative.[8][9]

Thiophene-2-carboxylic acid should be the final major metabolic product. It is very hydrophilic and is excreted in urine. Methiopropamine and especially thiopropamine are also excreted renally, unchanged.

Synthesis[edit]

There is a four-step synthesis of methiopropamine. It begins with (thiophen-2-yl)magnesium bromide, which is reacted with propylene oxide, yielding 1-(thiophen-2-yl)-2-hydroxypropane which is reacted with phosphorus tribromide, yielding 1-(thiophen-2-yl)-2-bromopropane which is finally reacted with methylamine, yielding 1-(thiophen-2-yl)-2-methylaminopropane.[10]

Four-step synthesis of racemic methiopropamine from (thiophen-2-yl)magnesium bromide.

Legality[edit]

Methiopropamine is not explicitly a controlled substance, however its legal status under the Federal Analog Act is not certain. It may be considered an analog of methamphetamine for legal purposes, although its structure differs more than previous successful prosecutions under the same law. It is explicitly illegal in Germany and the state of Florida.[11]

See also[edit]

References[edit]

  1. ^ Blicke, F. F.; Burckhalter, J. H. (1942). "α-Thienylaminoalkanes". Journal of the American Chemical Society 64 (3): 477–80. doi:10.1021/ja01255a001. 
  2. ^ Angelov, D; O'Brien, J; Kavanagh, P (2011). "The syntheses of 1-(2-thienyl)-2-(methylamino) propane (methiopropamine) and its 3-thienyl isomer for use as reference standards". Drug testing and analysis 5 (3): 145–9. doi:10.1002/dta.298. PMID 21770051. 
  3. ^ Methiopropamine Thread at UKChemicalResearch.org
  4. ^ Iversen, L.; Gibbons, S.; Treble, R.; Setola, V.; Huang, X. P.; Roth, B. L. (2012). "Neurochemical profiles of some novel psychoactive substances". European Journal of Pharmacology. doi:10.1016/j.ejphar.2012.12.006.  edit
  5. ^ Vree, T.B.; Gorgels, J.P.M.C.; Muskens, A.Th.J.M.; Van Rossum, J.M. (1971). "Deuterium isotope effects in the metabolism of n-alkylsubstituted amphetamines in man". Clinica Chimica Acta 34 (2): 333–44. doi:10.1016/0009-8981(71)90187-2. PMID 5113570. 
  6. ^ Treiber, Alexander; Dansette, Patrick M.; El Amri, Hamid; Girault, Jean-Pierre; Ginderow, Daria; Mornon, Jean-Paul; Mansuy, Daniel (1997). "Chemical and Biological Oxidation of Thiophene:  Preparation and Complete Characterization of Thiophene S-Oxide Dimers and Evidence for Thiophene S-Oxide as an Intermediate in Thiophene Metabolism in Vivo and in Vitro". Journal of the American Chemical Society 119 (7): 1565–71. doi:10.1021/ja962466g. 
  7. ^ Dansette, P.M.; Thang, Do Cao; Mansuy, H. El Amri D.; Mansuy, D (1992). "Evidence for thiophene-s-oxide as a primary reactive metabolite of thiophene in vivo: Formation of a dihydrothiophene sulfoxide mercapturic acid". Biochemical and Biophysical Research Communications 186 (3): 1624–30. doi:10.1016/S0006-291X(05)81594-3. PMID 1510686. 
  8. ^ Yamada, Hideyuki; Shiiyama, Sachiko; Soejimaohkuma, Toyomi; Honda, Shin-Ichiro; Kumagai, Yoshito; Cho, Arthur K.; Oguri, Kazuta; Yoshimura, Hidetoshi (1997). "Deamination of amphetamines by cytochromes P450: Studies on substrate specificity and regioselectivity with microsomes and purified CYP2C subfamily isozymes". The Journal of Toxicological Sciences 22 (1): 65–73. doi:10.2131/jts.22.65. PMID 9076658. 
  9. ^ Welter, J.; Meyer, M.R.; Wolf, E.U.; Weinmann, W.; Kavanaugh, P.; Maurer, H.H. (2013). "2-methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the rat and human using GC-MS and LC-(HR)-MS techniques". Analytical and Bioanalytical Chemistry 405 (10): 3125–3135. doi:10.1007/s00216-013-6741-4. PMID 23361230. 
  10. ^ Casale, John F.; Hays, Patrick A. (2011). "Methiopropamine: An Analytical Profile". Microgram Journal 8 (2): 53–7. 
  11. ^ "Methiopropamine (MPA)Legal Status". 2013-09-24. Retrieved 2013-10-16.