Bath salts, mephedrone, and methylenedioxypyrovalerone as emerging illicit drugs that will need targeted therapeutic intervention

Advances in Pharmacology

Volumn 69, Issue , 2014, Pages 581-620

  Glennon, Richard A ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

Author keywords

Amphetamine; Bath salts; Cathinone; Dopamine transporter; MDPV; Mephedrone; Methamphetamine; Methcathinone; Methylenedioxypyrovalerone; Methylone; Serotonin transporter; Aminophenones

Indexed keywords

3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4' METHYLMETHCATHINONE; AMPHETAMINE; BATH SALT; CATHA EDULIS EXTRACT; CATHINONE; COCAINE; EPHEDRA SINICA EXTRACT; METHCATHINONE; METHYLENEDIOXYPYROVALERONE; METHYLONE; NORPSEUDOEPHEDRINE; UNCLASSIFIED DRUG; ALKALOID; CENTRAL STIMULANT AGENT; DOPAMINE TRANSPORTER; DRUG DERIVATIVE; METHAMPHETAMINE; PYROVALERONE; PYRROLIDINE DERIVATIVE; SEROTONIN TRANSPORTER; STREET DRUG;

ARTICLE; CHEMICAL MODIFICATION; COMPLEX FORMATION; DRUG ABUSE; DRUG DISCRIMINATION; DRUG MECHANISM; DRUG METABOLISM; DRUG SYNTHESIS; HUMAN; LOCOMOTION; NEUROTRANSMITTER RELEASE; NOMENCLATURE; NONHUMAN; PRIORITY JOURNAL; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; ADDICTION; ANIMAL; BATH SALTS; CHEMISTRY; DRUG DELIVERY SYSTEM; MDPV; METABOLISM; REVIEW; Α-AMINOPHENONES;

AMPHETAMINE; BATH SALTS; CATHINONE; DOPAMINE TRANSPORTER; MDPV; MEPHEDRONE; METHAMPHETAMINE; METHCATHINONE; METHYLENEDIOXYPYROVALERONE; METHYLONE; SEROTONIN TRANSPORTER; Α-AMINOPHENONES;

ALKALOIDS; ANIMALS; CENTRAL NERVOUS SYSTEM STIMULANTS; DRUG DELIVERY SYSTEMS; HUMANS; METHAMPHETAMINE; PYRROLIDINES; STREET DRUGS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTANCE-RELATED DISORDERS;

EID: 84893168023     PISSN: 10543589     EISSN: 15578925     Source Type: Book Series    
DOI: 10.1016/B978-0-12-420118-7.00015-9     Document Type: Chapter

References (151)

1. Aarde S.M., Huang P.K., Creehan K.M., Dickerson T.J., Taffe M.A. The novel recreational drug 3,4-methylenedioxypyrovalerone (MDPV) is a potent psychomotor stimulant: Self-administration and locomotor activity in rats. Neuropharmacology 2013, 71:130-140.
2. Al-Hebshi N.N., Skaug N. Khat (Catha edulis)-An updated review. Addiction Biology 2002, 10:299-307.
3. Alles G.A., Fairchild M.D., Jensen M. Chemical pharmacology of Catha edulis. Journal of Medicinal and Pharmaceutical Chemistry 1961, 3:323-352.
4. Ammanna D., McLaren J.M., Gerostamoulos D., Beyer J. Detection and quantification of new designer drugs in human blood: Part 2-Designer cathinones. Journal of Analytical Toxicology 2012, 36:381-389.
5. Anderson, D. M., & Carrier, N. C. M. (2011). Khat: Social harms and legislation. A literature review. U. K. Home Office Report. ISBN: 978-1-84987-494-6.
6. Angoa-Perez M., Kane M.J., Fracescutti D.M., Sykes K.E., Shah M.M., Mohammed A.M., et al. Mephedrone, and abused psychoactive component of "bath salts" and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum. Journal of Neurochemistry 2012, 120:1097-1107.
7. 2A and α1B adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants. European Journal of Neuroscience 2004, 20:3073-3084.
8. Baumann M.H., Ayestas M.A., Partilla J.S., Sink J.R., Shulgin A.T., Daley P.F., et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Journal of Neuropsychopharmacology 2012, 37:1192-1203.
9. Berardelli A., Capocaccia L., Pacitti C., Tancredi V., Quinteri F., Elmi A. Behavioural and EEG effects induced by an amphetamine-like substance (cathinone) in rats. Pharmacological Research Communications 1980, 12:959-964.
10. Beyer J., Peters F.T., Kraemer T., Maurer H.H. Detection and validated quantification of nine herbal phenalkylamines and methcathinone in human blood plasma by LC-MS/MS with electrospray ionization. Journal of Mass Spectrometry 2007, 42:150-160.
11. Bockmuhl, M., & Gorr, G. (1936). Verfahren zur Darstellung von optisch active 1-aryl-2-amino-1-propanolen. German patent 639,126. November 28, 1936.
12. Boehringer Ingelheim. (1969). α-Substituted-ketones and processes for their preparation. British patent 1,149,366. April 23, 1969.
13. Bonano J., Glennon R.A., De Felice L.J., Banks M., Negus S.S. Abuse-related and abuse-limiting effects of methcathinone, and the synthetic "bath salts" cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology 2013, in press.
14. Bondareva T.S., Young R., Glennon R.A. Central stimulants as discriminative stimuli: Asymmetric generalization between (-)ephedrine and (S+)methamphetamine. Pharmacology, Biochemistry, and Behavior 2002, 74:157-162.
15. Borek H.A., Holstege C.P. Hyperthermia and multiorgan failure after abuse of "bath salts" containing 3,4-methylenedioxypyrovalerone. Annals of Emergency Medicine 2012, 60:103-105.
16. Brandt S.D., Freeman S., Sumnall H.R., Measham F., Cole J. Analysis of NRG 'legal highs' in the UK: Identification and formation of novel cathinones. Drug Testing and Analysis 2011, 3:569-575.
17. Brandt S.D., Sumnall H.R., Measham F., Cole J. Analyses of second-generation 'legal highs' in the UK: Initial findings. Drug Testing and Analysis 2010, 2:377-382.
18. Brenneisen R., Geisshüsler S., Schorno X. Metabolism of cathinone to (-)-norephedrine and (-)-norpseudoephedrine. Journal of Pharmacy Pharmacology 1986, 38:298-300.
19. Cameron K.N., Kolanos R., Solis E., Glennon R.A., De Felice L.J. Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. British Journal of Pharmacology 2013, 68:1750-1757.
20. Cameron K., Kolanos R., Vekariya R., De Felice L., Glennon R.A. Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of "bath salts", produce opposite effects at the human dopamine transporter. Psychopharmacology 2013, 227:493-499.
21. Chen K.K., Kao C.H. Ephedrine and pseudoephedrine, their isolation, constitution, isomerism, properties, derivatives, and synthesis. Journal of the American Pharmaceutical Association 1926, 15:625-639.
22. Coppola M., Mondola R. 3.4-Methylenedioxypyrovalerone (MDPV): Chemistry, pharmacology and toxicology of a new designer drug of abuse marketed online. Toxicology Letters 2012, 208:12-15.
23. Cozzi N.V., Brandt S.D., Daley P.F., Partilla J.S., Rothman R.B., Tulzer A., et al. Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs. European Journal of Pharmacology 2013, 699:180-187.
24. Cozzi N.V., Sievert M.K., Shulgin A.T., Jacob P., Ruoho A.E. Inhibition of plasma membrane monoamine transporters by β-ketoamphetamines. European Journal of Pharmacology 1999, 381:63-69.
25. Dal Cason T.A., Young R., Glennon R.A. Cathinone: An investigation of several N-alkyl and methylenedioxy analogs. Pharmacology, Biochemistry, and Behavior 1997, 58:1109-1116.
26. Dybdal N.F., Holder N.D., Ottoson P.E., Sweeney M.D., Williams T. Mephedrone: Public health risk, mechanisms of action, and behavioral effects. European Journal of Pharmacology 2013, 714:32-40.
27. Eberhard A. Ueber das Ephedrine und verwante Verbindugen. Archivs die Pharmazie 1915, 253:62-91.
28. Eberhard A. Ueber die Synthese des inaktiven Ephedrine bez. Pseudoephedrins. Archivs die Pharmazie 1920, 258:97-129.
29. Eshleman A.J., Wofrum K.M., Hatfield M.G., Johnson R.A., Murphy K.V., Janowsky A. Substituted methcathinones differ in transporter and receptor interactions. Biochemical Pharmacology 2013, 85:1803-1815.
30. Fantegrossi W.E., Gannon B.M., Zimmerman S.M., Rice K.C. In vivo effects of abused 'bath salt' constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: Drug discrimination, thermoregulation, and locomotor activity. Neuropsychopharmacology 2013, 38:563-573.
31. Federal Register Schedules of controlled substances: Temporary placement of three synthetic cathinones into Schedule I. Federal Register 2011, 76:65371-65375.
32. Fellows L. East Africa turns on with khat 1967, New York Times, July 9, 1967.
33. Fitzgerald, J. (2009). Khat: A literature review. http://www.ceh.org.au/downloads/khat_report_final.pdf.
34. Foley K.F., Cozzi N.V. Novel aminopropiophenones as potential antidepressants. Drug Development Research 2003, 60:252-260.
35. Fourneau E., Kanao S. Sur la synthese l'ephedrine. Bulletin de la Sociétée chimique de France 1924, 35:614-625.
36. Friebel H., Brilla R. Über den zentralerregenden Wirkstoff der frischen Blätter und Zweigspitzen von Catha edulis Forskal. Naturwissenschaften 1963, 50:354-355.
37. Fuwa T., Fukumori N., Tanaka T., Kubo Y., Ogata A., Uehara S., et al. Microdialysis study of drug effects on central nervous system: Changes of dopamine levels in mice striatum after oral administration of methylenedioxypyrovalerone. Annual Report Tokyo Metropolitan Institute of Public Health 2007, 58:287-292.
38. Gatch M.B., Taylor C.M., Forster M.J. Locomotor stimulant and discriminative stimulus effects of "bath salt" cathinones. Behavioral Pharmacology 2013, 24:437-447.
39. Gaulier J.M., Canal M., Pradeille J.L., Marquet P., Lachâtre G. New drugs at "rave parties": Ketamine and prolintane. Acta Clinica Belgica. Supplementum 2002, 41-46.
40. Gil D., Adamowicz P., Skulska A., Tokarczyk B., Stanaszek R. Analysis of 4-MEC in biological and non-biological material-three case reports. Forensic Science International 2013, 228:e11-e15.
41. Glennon R.A. Discriminative stimulus properties of phenylisopropylamine derivatives. Drug and Alcohol Dependence 1986, 17:119-134.
42. Glennon R.A. Classical hallucinogens. Handbook of experimental pharmacology: Pharmacological aspects of drug dependence 1996, 343-371. Springer Verlag, Basel, Switzerland. C.R. Schuster, M.J. Kuhar (Eds.).
43. Glennon R.A. Hallucinogens, stimulants, and related drugs of abuse. Foye's principles of medicinal chemistry 2008, 631-651. Lippincott, Williams & Wilkins, Baltimore, MD. 5th ed. D.A. Williams, T.L. Lempke, V.F. Roche, S.W. Zito (Eds.).
44. Glennon R.A., Ismaiel A.M., Martin B., Poff D., Sutton M. A preliminary behavioral investigation of PMMA, the 4-methoxy analog of methamphetamine. Pharmacology, Biochemistry, and Behavior 1988, 31:9-13.
45. Glennon R.A., Schechter M.D., Rosecrans J.A. Discriminative stimulus properties of S(-)- and R(+)-cathinone, (+)-cathine and several structural modifications. Pharmacology, Biochemistry, and Behavior 1984, 21:1-3.
46. Glennon R.A., Showalter D. The effect of cathinone and several related derivatives on locomotor activity. Research Communications on Substance Abuse 1981, 2:186-192.
47. Glennon R.A., Young R. Drug discrimination: Applications to medicinal chemistry and drug studies 2011, John Wiley and Sons, Inc, Hoboken.
48. Glennon R.A., Young R., Hauck A.E. Structure-activity studies on methoxy-substituted phenylisopropylamines using drug discrimination methodology. Pharmacology, Biochemistry, and Behavior 1985, 22:723-729.
49. Glennon R.A., Young R., Hauck A.E., McKenney J.D. Structure-activity studies of amphetamine analogs using drug discrimination methodology. Pharmacology, Biochemistry, and Behavior 1984, 21:895-901.
50. Glennon R.A., Young R., Martin B.R., Dal Cason T.A. Methcathinone ("Cat"): An enantiomeric potency comparison. Pharmacology, Biochemistry, and Behavior 1995, 50:601-606.
51. Glennon R.A., Yousif M., Naiman N.A., Kalix P. Methcathinone: A new and potent amphetamine-like agent. Pharmacology, Biochemistry, and Behavior 1987, 26:547-551.
52. Goudie A.J., Atkinson J., West C.R. Discriminative properties of the psychostimulant dl-cathinone in a two lever operant task. Lack of evidence for dopaminergic mediation. Neuropharmacology 1986, 25:85-94.
53. Hadlock G.C., Webb K.M., McFadden L.M., Chu P.W., Ellis J.D., Allen S.C., et al. 4-Methylmethcathinone (mephedrone): Neuropharmacological effects of a designer stimulant of abuse. The Journal of Pharmacology and Experimental Therapeutics 2011, 339:530-536.
54. Halbach H. Medical aspects of the chewing of khat leaves. Bulletin of the World Health Organization 1972, 47:21-29.
55. Heinzelman R.V., Aspergren D.B. Compounds containing the pyrrolidine ring: Analogs of sympathomimetic amines. Journal of the American Chemical Society 1953, 75:3409-3413.
56. Higgs R.A., Glennon R.A. Stimulus properties of ring-methyl amphetamine analogs. Pharmacology, Biochemistry, and Behavior 1990, 37:835-837.
57. Hollister L.E., Gillespie H.K. A new stimulant, prolintane hydrochloride, compared with dextroamphetamine in fatigued volunteers. The Journal of Clinical Pharmacology 1970, 10:103-109.
58. Huang P.K., Aarde S.M., Angrish D., Houseknecht K.L., Dickerson T.J., Taffe M.A. Contrasting effects of d-methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug and Alcohol Dependence 2012, 126:168-175.
59. Hyde J.F., Browning E., Adams R. Synthetic homologs of d,l-ephedrine. Journal of the American Chemical Society 1928, 50:2287-2292.
60. Iversen, L. E. (2010). Consideration of the cathinones. Advisory Council on the Misuse of Drugs. A report submitted to the Home Secretary of the UK (March 31, 2010).
61. Iversen L., Gibbons S., Treble R., Setola V., Huang X.P., Roth B.L. Neurochemical profiles of some novel psychoactive substances. European Journal of Pharmacology 2013, 700:147-151.
62. Iwao J., Kowaki C., Rakemi H. Studies on alkanolamines. II. Synthesis of N-methylephedrone and its derivatives. Application of the Viogt reaction. Yakugaku Zasshi 1954, 74:551-553.
63. Jacob, P., & Shulgin, A. T. (1996). Novel N-substituted 2-amino-3',4'-methylenedioxy-propiophenones. WO patent 9639133. December 12, 1996.
64. Kalix P. Hypermotility of the amphetamine type induced by a constituent of khat leaves. British Journal of Pharmacology 1980, 68:11-13.
65. Kalix P. Hyperthermic response to (-)cathinone, an alkaloid of Catha edulis (khat). Journal of Pharmacy and Pharmacology 1980, 32:662-663.
66. Kalix P. Cathinone, an alkaloid from khat leaves with an amphetamine-like releasing effect. Psychopharmacology 1981, 74:269-270.
67. Kalix P. Cathinone, a natural amphetamine. Pharmacology and Toxicology 1992, 70:77-86.
68. Kalix P., Braeden O. Pharmacological aspects of the chewing of khat leaves. Pharmacological Reviews 1985, 37:149-164.
69. Kalix P., Glennon R.A. Further evidence for an amphetamine-like mechanism of action of the alkaloid cathinone. Biochemical Pharmacology 1986, 35:3015-3019.
70. Kamata H.T., Shima N., Zaitsu K., Kamata T., Miki A., Nishikawa M., et al. Metabolism of the recently encountered designer drug, methylone, in humans and rats. Xenobiotica 2006, 36:709-723.
71. Karila L., Reynaud M. GHB and synthetic cathinones: Clinical effects and potential consequences. Drug Testing and Analysis 2010, 3:552-559.
72. Kasick D.P., McKnight C.A., Kilsovic E. "Bath salt" ingestion leading to severe intoxication delirium: Two cases and a brief review of the emergence of mephedrone use. Clinical Toxicology 2012, 38:176-180.
73. Katz J.L., Ricaurte G.A., Witkin J.M. Reinforcing effects of enantiomers of N,N-dimethylamphetamine in squirrel monkeys. Psychopharmacology 1992, 107:315-318.
74. Kehr J., Ichinose F., Yoshitake S., Goiny M., Sievertsson T., Nyberg F., et al. Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. British Journal of Pharmacology 2011, 164:1949-1958.
75. Kelly J.P. Cathinone derivatives: A review of their chemistry, pharmacology and toxicology. Drug Testing and Analysis 2011, 3:439-453.
76. Kennedy J.G., Teague J., Fairbanks L. Qat use in North Yemen and the problem of addiction: A study in medical anthropology. Culture, Medicine and Psychiatry 1980, 4:311-344.
77. Knoll J. Studies on the central effects of (-)cathinone. NIDA Research Monograph 1979, 27:322-323.
78. Kolanos R., Cameron K.N., Vekariya R.H., De Felice L.J., Glennon R.A. "Bath salts": An imitation of methamphetamine plus cocaine? 2011.
79. Kolanos, R., Solis, E., Sakloth, F., De Felice, L. J., & Glennon, R. A. (2013). 'Deconstruction' of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. ACS Chemical Neuroscience, in press. Unpublished data, manuscript submitted for publication.
80. Köppe, H., Ludwig, G., & Zeile, K. (1969). 1-(3'4'-Methylenedioxy-phenyl)-2-pyrrolidino-alkanones-(1). U.S. Patent 3,478,050, November 11, 1969.
81. Kraemer T., Maurer H.H. Toxicokinetics of amphetamines: Metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Therapeutic Drug Monitoring 2002, 24:277-289.
82. Kuitunen T., Kärkkäinen S., Ylitalo P. Comparison of the acute physical and mental effects of ephedrine, fenfluramine, phentermine and prolintane. Methods and Findings in Experimental and Clinical Pharmacology 1984, 6:265-270.
83. Kyle P.B., Daley W.P. Domestic abuse of the European rave drug prolintane. Journal of Analytical Toxicology 2007, 31:415-418.
84. Lee M.R. The history of ephedra (ma-huang). The Journal of the Royal College of Physicians of Edinburg 2011, 41:78-84.
85. Lee S., Yoo H.H., In M.K., Jin C., Kim D.H. Stereoselectivity in the cytochrome P450-dependent N-demethylation and flavin monooxygenase-dependent N-oxidation of N,N-dimethylamphetamine. Archives of Pharmacal Research 2013, 36:1385-1391.
86. Lin T.C., Lin D.L., Lua A.C. Detection of p-chloroamphetamine in urine samples with mass spectrometry. Journal of Analytical Toxicology 2011, 35:205-210.
87. L'Italien, Y. J., Park, H., & Rebstock, L. C. (1957). Methylaminopropiophenone compounds and methods for producing the same. US patent 2,802,865, August 13, 1957.
88. Ljungberg T., Ungerstedt U. A rapid and simple behavioural screening method for simultaneous assessment of limbic and striatal blocking effects of neuroleptic drugs. Pharmacology, Biochemistry, and Behavior 1985, 23:479-485.
89. Loh H.H., Tseng L.-F. Role of biogenic amines in the actions of methoxyamphetamines. The psychopharmacology of hallucinogens 1978, 13-22. Pergamon Press, New York. R.C. Stillman, R.E. Willette (Eds.).
90. López-Arnau R., Martinez-Clemente J., Pubill D., Escubedo E., Camarasa J. Comparative neuropharmacology of three psychostimulant cathinone derivatives: Butylone, mephedrone and methylone. British Journal of Pharmacology 2012, 167:407-420.
91. Marinetti L.J., Antonides H.M. Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: Method development, drug distribution and interpretation of results. Journal of Analytical Toxicology 2013, 37:135-146.
92. Markantonis S.L., Kyroudis A., Beckett A.H. The in vitro reduction of dimethylpropion. Biochemical Medicine and Metabolic Biology 1989, 42:1-8.
93. Martínez-Clemente J., Escubedo E., Pubill D., Camarasa J. Interaction of mephedrone with dopamine and serotonin targets in rats. European Neuropsychopharmacology 2012, 22:231-236.
94. Marusich J.A., Grant K.R., Blough B.E., Wiley J.L. Effects of synthetic cathinones contained in "bath salts" on motor behavior and a functional observational battery in mice. NeuroToxicology 2012, 33:1305-1313.
95. Meltzer P.C., Butler D., Deschamps J.R., Madras B.K. 1-(4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (pyrovalerone) analogs. A promising class of monoamine uptake inhibitors. Journal of Medicinal Chemistry 2006, 49:1420-1432.
96. Meyer M.R., Du P., Schuster F., Maurer H.H. Studies on the metabolism of the α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS. Journal of Mass Spectrometry 2010, 45:1426-1442.
97. Motbey C.P., Hunt G.E., Bowen M.T., Artiss S., McGregor I.S. Mephedrone (4-methylmethcathinone, 'meow'): Acute behavioural effects and distribution of Fos expression in adolescent rats. Addiction Biology 2011, 17:409-422.
98. Negus S.S., Banks M.L. Making the right choice: Lessons from drug discrimination, for research on drug reinforcement and drug self-administration. Drug discrimination: Applications to medicinal chemistry and drug studies 2011, 361-388. John Wiley and Sons, Inc, Hoboken. R.A. Glennon, R. Young (Eds.).
99. Nicholson A.N., Stone B.M., Jones M.M. Wakefulness and reduced rapid eye movement sleep: Studies with prolintane and pemoline. British Journal of Clinical Pharmacology 1980, 10:465-472.
100. Paul B.D., Cole K.A. Cathinone (Khat) and methcathinone (CAT) in urine specimens: A gas chromatographic-mass spectrometric detection procedure. Journal of Analytical Toxicology 2001, 25:525-530.
101. Pawlik E., Plässer G., Mahler H., Daldrup T. Studies on the phase I metabolism of the new designer drug 3-fluoromethcathinone using rabbit liver slices. International Journal of Legal Medicine 2012, 126:231-240.
102. Payá B., Guisado J.A., Vaz F.J., Crespo-Facorro B. Visual hallucinations induced by the combination of prolintane and diphenhydramine. Pharmacopsychiatry 2002, 35:24-25.
103. Penders T.M., Gestring R.E., Vilensky D.A. Intoxication delirium following use of synthetic cathinone derivatives. Clinical Toxicology 2012, 38:616-617.
104. Prosser J.M., Nelson L.S. The toxicology of bath salts: A review of synthetic cathinones. Journal of Medical Toxicology 2012, 8:33-42.
105. Ristic S., Thomas A. On the constituents of Catha edulis. Archives die Pharmazie 1962, 295:524-525.
106. Rosecrans J.A., Campbell O.L., Dewey W.L., Harris L.S. Discriminative stimulus and neurochemical mechanism of cathinone: A preliminary study. NIDA Research Monograph 1979, 27:328-329.
107. Rösner P., Quednow B., Girreser U., Junge T. Isomeric fluoro-methoxy-phenylalkylamines: A new series of controlled-substance analogues (designer drugs). Forensic Science International 2005, 148:143-156.
108. Rothman R.B., Vu N., Partilla J.S., Roth B.L., Hufeisen S.J., Compton-Toth B.A., et al. In vitro characterization of ephedrine-related stereoisomers at biogenic amine transporters and the receptorome reveals selective actions as norepinephrine transporter substrates. The Journal of Pharmacology and Experimental Therapeutics 2003, 307:138-145.
109. Savenko, V. G., Semkin, E. P., Sorokin, V. I., & Kazankov, S. P. (1989). Expert examination of narcotic substances obtained from ephedrine. Ministry of the Interior, All-Union Scientific Research Institute Report, pp. 1-22.
110. Schechter M.D., Glennon R.A. Cathinone, cocaine and methamphetamine: Similarity of behavioral effects. Pharmacology, Biochemistry, and Behavior 1985, 22:913-916.
111. Schorno, X., & Steinegger, E. (1978). The phenylalkylamines of Catha edulis Forsk. The absolute configuration of cathinone. United Nations Laboratory document MNAR/7/1978, GE. 78-3956.
112. Schütte, J. (1961). Anorexigenic propiophenones. U. S. patent 3,001,910. September 26, 1961.
113. Seeger, E. (1964). Verfahren zur Herstellung von α-Pyrrolidinoketonen und deren Salzen. German patent 1,161,274. January 16, 1964.
114. Shapiro D. Benzoisoquinoline studies. Part I. Open-ring models of 4-benzylisoquinolines. Journal of Organic Chemistry 1950, 15:1027-1036.
115. Shulgin A., Shulgin A. Pihkal 1991, Transform Press, Berkeley, CA.
116. Sikk K., Haldre S., Aquilonius S.M., Asser A., Paris M., Roose A., et al. Manganese-induced parkinsonism in methcathinone abusers: Bio-markers of exposure and follow-up. European Journal of Neurology 2013, 20:915-920.
117. Simmler L.D., Buser T.A., Donzelli M., Schramm Y., Dieu L.-H., Huwyler J., et al. Pharmacological characterization of designer cathinones in vitro. British Journal of Pharmacology 2012, 168:458-470.
118. Spiller H.A., Ryan M.L., Weston R.G., Jansen J. Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States. Clinical Toxicology 2011, 49:499-505.
119. Springer D., Fritschi G., Maurer H.H. Metabolism and toxicological detection of the new designer drug 3,4-methylenedioxy-α-pyrrolidinopropiophenone studied in urine using gas chromatography-mass spectrometry. Journal of Chromatography B 2003, 793:377-388.
120. Springer D., Fritschi G., Maurer H.H. Metabolism of the new designer drug alpha-pyrrolidinopropiophenone (PPP) and the toxicological detection of PPP and 4-methyl-alpha-pyrrolidinopropiophenone (MPPP) studied in rat urine using gas chromatography-mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 2003, 796:253-266.
121. Springer D., Paul L.D., Staack R.F., Kraemer T., Maurer H.H. Identification of cytochrome P450 enzymes involved in the metabolism of 4-methyl-α-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes. The American Society for Pharmacology and Experimental Therapeutics 2003, 31:979-982.
122. Springer D., Peters F.T., Fritschi G., Maurer H.H. Studies on the metabolism and toxicological detection of the new designer drug 4-methyl-α-pyrrolidinopropiophenone in urine using gas chromatography-mass spectrometry. Journal of Chromatography B 2002, 773:25-33.
123. Springer D., Staack R.F., Paul L.D., Kraemer T., Maurer H.H. Identification of cytochrome P450 enzymes involved in the metabolism of 4'-methoxy-α-pyrrolidinopropiophenone (MOPPP), a designer drug, in human liver microsomes. Xenobiotica 2003, 33:989-998.
124. Strano-Rossi S., Cadwallader A.B., de la Torre X., Botrè F. Toxicological determination and in vitro metabolism of the designer drug methylenedioxypyrovalerone (MPDV) by gas chromatography/mass spectrometry and liquid chromatography/ quadrupole time-of-flight mass spectrometry. Rapid Communications in Mass Spectrometry 2010, 24:2706-2714.
125. Testa B., Salvesen B. Quantitative structure-activity relationships in drug metabolism and disposition: Pharmacokinetics of N-substituted amphetamines in humans. Journal of Pharmaceutical Sciences 1980, 69:497-501.
126. Thevis M., Sigmund G., Thomas A., Gougoulidis V., Rodchenkov G., Schanzer W. Doping control analysis of metamfepramone and two major metabolites using liquid chromatography-tandem mass spectrometry. European Journal of Mass Spectrometry 2009, 15:507-515.
127. Thomae, K. (1959). Improvements in or relating to tertiary amines and their salts and the production thereof. UK patent GB814153. May 27, 1959.
128. Thornton S.L., Gerona R.R., Tomaszewski C.A. Psychosis from a bath salt product containing flephedrone and MDPV with serum, urine, and product quantification. Journal of Medical Toxicology 2012, 8:310-313.
129. UN Document. (1975). Studies on the chemical composition of khat. III. Investigations on the phenylalkylamine fraction. United Nations Laboratory document MNAR/11/75, GE. 75-1264.
130. UN Document. (1978). Note on the synthesis of cathinone and its "dimer" (3,6-dimethyl-2,5-diphenylpyrazine). United Nations Laboratory document MNAR/3/1978, GE. 78-1836.
131. UN Document. (1979). The botany and chemistry of khat. United Nations Laboratory document MNAR/3/1979, GE. 79-10365.
132. UNODC. (2013). The challenge of new psychoactive substances. A report from the United Nations Office on Drugs and Crime. Vienna, Austria, pp 1-56.
133. van der Schoot J.B., Ariens E.J., van Rossum J.M., Hurkmans J.A.T.M. Phenylisopropylamine derivatives, structure and action. Arznemittel-Forschung 1962, 12:902-907.
134. Varner K.J., Daigle K., Weed P.F., Lewis P.B., Mahne S.E., Sankaranarayanan A., et al. Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats. Psychopharmacology (Berlin) 2012, 225:675-685.
135. Wander, A. (1963). α-Pyrrolidino-valerophenones. British patent 927,475. May 29, 1963.
136. Watterson L.R., Kufahl P.R., Nemirovsky N.E., Sewalia K., Grabenauer M., Thomas B.F., et al. Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Addiction Biology 2013, 10.1111/j.1369-1600.2012.00474.x.
137. Wee S., Anderson K.G., Baumann M.H., Rothman R.B., Blough B.E., Woolverton W.L. Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs. The Journal of Pharmacology and Experimental Therapeutics 2005, 313:848-854.
138. Westphal F., Junge T., Rösner P., Fritschi G., Klein B., Girreser U. Mass spectral and NMR spectral data of two new designer drugs with an α-aminophenone structure: 4'-Methyl-α-pyrrolidinohexanophenone and 4'-methyl-α-pyrrolidinobutyrophenone. Forensic Science International 2007, 169:32-42.
139. Wolfes O. Über das Vorkommen von d-nor-iso-Ephedrin in Catha edulis. Archives die Pharmazie 1930, 268:81-83.
140. Wood D.M., Davies S., Greene S.L., Button J., Holt D.W., Ramsey J., et al. Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology 2010, 48:924-927.
141. Woolverton W.L. Discriminative stimulus effects of cocaine. Drug discrimination: Applications to drug abuse research 1991, 61-74. National Institute on Drug Abuse, Rockville, MD. R.A. Glennon, T.U.C. Jarbe, J. Frankenheim (Eds.).
142. Woolverton W.L., Shybut G., Johanson C.E. Structure-activity relationships among some d-N-alkylated amphetamines. Pharmacology, Biochemistry, and Behavior 1980, 13:869-876.
143. Yanagita T. Studies on cathinones: Cardiovascular and behavioral effects in rats and self-administration experiment in Rhesus monkeys. NIDA Research Monograph 1979, 27:326-327.
144. Young R., Glennon R.A. Discriminative stimulus properties of amphetamine and structurally related phenalkylamines. Medicinal Research Reviews 1986, 6:99-130.
145. Young R., Glennon R.A. Cocaine-stimulus generalization to two new designer drugs: Methcathinone and 4-methylaminorex. Pharmacology, Biochemistry, and Behavior 1993, 45:229-231.
146. Young R., Glennon R.A. A three-lever operant procedure differentiates the stimulus effects of R(-)-MDA from S(+)-MDA. Journal of Pharmacology and Experimental Therapeutics 1996, 276:594-601.
147. Young R., Glennon R.A. Discriminative stimulus effects of S(-)-methcathinone (CAT): A potent stimulant drug of abuse. Psychopharmacology 1998, 140:250-256.
148. Zaitsu K., Katagi M., Kamata H.T., Kamata T., Shima N., Miki A., et al. Determination of the metabolites of the new designer drugs bk-MBDB and bk-MDEA in human urine. Forensic Science International 2009, 188:131-139.
149. Zaitsu K., Katagi M., Kamata T., Kamata H., Shima N., Tsuchihashi H., et al. Determination of a newly encountered designer drug "p-methoxyethylamphetamine" and its metabolites in human urine and blood. Forensic Science International 2008, 177:77-84.
150. Zawilska J.B., Wojcieszak J. Designer cathinones-An emerging class of novel recreational drugs. Forensic Science International 2013, 231:42-53.
151. Zhingel K.Y., Dovensky W., Crossman A., Allen A. Ephedrone: 2-Methylamino-1-phenylpropan-1-one. Journal of Forensic Sciences 1991, 36:915-920.