Synthesis, characterization, and monoamine transporter activity of the new psychoactive substance 3',4'-methylenedioxy-4-methylaminorex (MDMAR)

Drug Testing and Analysis

Volumn 7, Issue 7, 2015, Pages 555-564

  Mclaughlin, Gavin ^a,b   Morris, Noreen ^a   Kavanagh, Pierce V ^b   Power, John D ^b,c   Twamley, Brendan ^d   O'Brien, John ^d   Talbot, Brian ^d   Dowling, Geraldine ^e   Mahony, Olivia ^f   Brandt, Simon D ^g   Patrick, Julian ^h   Archer, Roland P ⁱ   Partilla, John S ^j   Baumann, Michael H ^j  

^a Athletic Rehabilitation Therapy Ireland   (Ireland)

^b ST JAMES S HOSPITAL   (Ireland)

^c Forensic Science Laboratory Dulin Ireland   (Ireland)

^d TRINITY COLLEGE DUBLIN   (Ireland)

^e Backweston Lab Complex   (Ireland)

^f DUBLIN INSTITUTE OF TECHNOLOGY   (Ireland)

^g LIVERPOOL JOHN MOORES UNIVERSITY   (United Kingdom)

^h Scientific Supplies Ltd   (United Kingdom)

ⁱ Longue Rue St Martin's   (United Kingdom)

^j NATIONAL INSTITUTE ON DRUG ABUSE   (United States)

more..

Author keywords

4,4' DMAR; Aminorex; Forensic; New psychoactive substances; Psychostimulants

Indexed keywords

AMINES; CRYSTAL STRUCTURE; DRUG PRODUCTS; FORENSIC SCIENCE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PLANTS (BOTANY); SPECTROSCOPIC ANALYSIS;

4,4'-DIMETHYLAMINOREX; AMINOREX; CIS-ISOMERS; CRYSTAL STRUCTURE ANALYSIS; FORENSIC; METHYLENEDIOXYMETHAMPHETAMINE; NEW PSYCHOACTIVE SUBSTANCE; ONLINE VENDORS; PSYCHOSTIMULANTS; RELEASING AGENT;

GAS CHROMATOGRAPHY;

3',4' METHYLENEDIOXY 4 METHYLAMINOREX; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; CARRIER PROTEIN; DOPAMINE TRANSPORTER; MONOAMINE; MONOAMINE TRANSPORTER; NEW DRUG; NORADRENALIN TRANSPORTER; PSYCHOTROPIC AGENT; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; AMINOREX; CENTRAL STIMULANT AGENT; VESICULAR MONOAMINE TRANSPORTER;

ANIMAL TISSUE; ARTICLE; BRAIN TISSUE; CIS ISOMER; CONTROLLED STUDY; CRYSTAL STRUCTURE; DRUG STRUCTURE; DRUG SYNTHESIS; ELECTROSPRAY MASS SPECTROMETRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ISOMERIZATION; MALE; MASS FRAGMENTOGRAPHY; MONOAMINE RELEASE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; PROTEIN FUNCTION; QUADRUPOLE MASS SPECTROMETRY; RAT; TRANS ISOMER; X RAY CRYSTALLOGRAPHY; ANALOGS AND DERIVATIVES; ANIMAL; DRUG EFFECTS; METABOLISM; SPRAGUE DAWLEY RAT; SYNAPTOSOME; SYNTHESIS;

AMINOREX; ANIMALS; CENTRAL NERVOUS SYSTEM STIMULANTS; CRYSTALLOGRAPHY, X-RAY; MALE; PSYCHOTROPIC DRUGS; RATS; RATS, SPRAGUE-DAWLEY; SYNAPTOSOMES; VESICULAR MONOAMINE TRANSPORT PROTEINS;

EID: 84937693453     PISSN: 19427603     EISSN: 19427611     Source Type: Journal    
DOI: 10.1002/dta.1732     Document Type: Article

References (30)

1. EMCDDA-Europol. Joint Report on a new psychoactive substance: 4, 4'-DMAR (4-methyl-5-(4-methylphenyl)-4, 5- dihydrooxazol-2-amine), Joint Reports. 2014. Publications Office of the European Union, Luxembourg. Available at: http://www.emcdda.europa.eu/attachements.cfm/att_229825_EN_TDAS14006ENN.pdf [21 July 2014].
2. S. Cosbey, S. Kirk, M. McNaul, L. Peters, B. Prentice, A. Quinn, S.P. Elliott, S.D. Brandt, R.P. Archer . Multiple fatalities involving a new designer drug: para-methyl-4-methylaminorex. J. Anal. Toxicol. 2014, 38, 383.
3. Council of the European Union. Request for risk assessment on new psychoactive substance 4, 4'-DMAR (4-methyl-5-(4-methylphenyl)-4, 5-dihydrooxazol-2-amine). 2014. Available at: http://register.consilium.europa.eu/doc/srv?l=EN&f=ST10619 2014 INIT [21 July 2014].
4. F.T. Davis, M.E. Brewster . A fatality involving U4Euh, a cyclic derivative of phenylpropanolamine. J. Forensic Sci. 1988, 33, 549.
5. S.D. Brandt, M.H. Baumann, J.S. Partilla, P.V. Kavanagh, J.D. Power, B. Talbot, B. Twamley, J. O'Brien, O. Mahony, S.P. Elliott, R.P. Archer, J. Patrick, K. Singh, N.M. Dempster, S.H. Cosbey . Characterization of a novel and potentially lethal designer drug, (±)-cis-para-methyl-4-methylaminorex (4, 4'-DMAR, or 'Serotoni'). Drug Test. Anal. 2014, 6, 684.
6. G.I. Poos, J.R. Carson, J.D. Rosenau, A.P. Roszkowski, N.M. Kelley, J. McGowin . 2-Amino-5-aryl-2-oxazolines. Potent new anorectic agents. J. Med. Chem. 1963, 6, 266.
7. J.R. Carson, G.I. Poos, H.R. Almond Jr. 2-Amino-5-aryl-2-oxazolines. Tautomerism, stereochemistry, and an unusual reaction. J. Org. Chem. 1965, 30, 2225.
8. F. Follath, F. Burkart, W. Schweizer . Drug-induced pulmonary hypertension? Br. Med. J. 1971, 1, 265.
9. H.P. Gurtner . Aminorex and pulmonary hypertension. A review. Cor Vasa 1985, 27, 160.
10. United Nations. Convention on Psychotropic Substances, 1971. Available at: http://www.unodc.org/pdf/convention_1971_en.pdf [25 March 2014].
11. EMCDDA-Europol. Dangerous synthetic drugs hit the EU market. Available at: http://www.emcdda.europa.eu/news/2014/europol-emcdda1 [05 March 2014].
12. R.B. Rothman, M.A. Ayestas, C.M. Dersch, M.H. Baumann . Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Circulation 1999, 100, 869.
13. R.B. Rothman, M.H. Baumann . Monoamine transporters and psychostimulant drugs. Eur. J. Pharmacol. 2003, 479, 23.
14. T. Hofmaier, A. Luf, A. Seddik, T. Stockner, M. Holy, M. Freissmuth, G.F. Ecker, R. Schmid, H.H. Sitte, O. Kudlacek . Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters. Neurochem. Int. 2014, 73, 32.
15. M.H. Baumann, X. Wang, R.B. Rothman . 3, 4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: A reappraisal of past and present findings. Psychopharmacology (Berl) 2007, 189, 407.
16. APEX2 program suite, Bruker AXS Inc., Madison, Wisconsin, USA, 2012.
17. G.M. Sheldrick . A short history of SHELX. Acta Crystallogr. A 2008, 64, 112.
18. R.B. Rothman, N. Vu, J.S. Partilla, B.L. Roth, S.J. Hufeisen, B.A. Compton-Toth, J. Birkes, R. Young, R.A. Glennon . In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. J. Pharmacol. Exp. Ther. 2003, 307, 138.
19. M.H. Baumann, M.A. Ayestas Jr., J.S. Partilla, J.R. Sink, A.T. Shulgin, P.F. Daley, S.D. Brandt, R.B. Rothman, A.E. Ruoho, N.V. Cozzi . The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 2012, 37, 1192.
20. Serotoni. Available at: http://serotoni.info [22 July 2014].
21. D.A. Cooper, in Proceedings of the international symposium on the forensic aspects of controlled substances: March 28 - April 1, 1988, (Ed: R.T. Castonguay ). Laboratory Division, Federal Bureau of Investigation, U.S. Dept. of Justice, Washington, DC, 1988, pp. 79.
22. Bluelight. 2008, Thread: Substituted Aminorex Series. Available at: http://www.bluelight.org/vb/threads/367053-Substituted-Aminorex-Series [28 May 2014].
23. G. Fodor, K. Koczka . 155. The stereochemical course of the conversion of 2-ureidoalcohols into oxazolidines. Part I. J. Chem. Soc. 1952, 850.
24. W.R. Rodriguez, R.A. Allred . Synthesis of trans-4-methylaminorex from norephedrine and potassium cyanate. Microgram. J. 2005, 3, 154.
25. A. Cruz, I.I. Padilla-Martínez, E.V. García-Báez, R. Contreras . Reactivity of chlorodeoxypseudoephedrines with oxo-, thio-, and selenocyanates. Tetrahedron: Asymmetry 2007, 18, 123.
26. R.F.X. Klein, A.R. Sperling, D.A. Cooper, T.C. Kram . The stereoisomers of 4-methylaminorex. J. Forensic Sci. 1989, 34, 962.
27. G.L. Henderson, M.R. Harkey, Y.T. Chueh . Metabolism of 4-methylaminorex (" EU4EA" ) in the rat. J. Anal. Toxicol. 1995, 19, 563.
28. S.L. Hill, S.H. Thomas . Clinical toxicology of newer recreational drugs. Clin. Toxicol. (Phila.) 2011, 49, 705.
29. L.J. Schep, R.J. Slaughter, D.M. Beasley . The clinical toxicology of metamfetamine. Clin. Toxicol. (Phila.) 2010, 48, 675.
30. S.D. Brandt, L.A. King, M. Evans-Brown . The new drug phenomenon. Drug Test. Anal. 2014, 6, 587.