The preclinical pharmacology of mephedrone; Not just MDMA by another name

British Journal of Pharmacology

Volumn 171, Issue 9, 2014, Pages 2251-2268

  Green, A R ^a   King, M V ^a   Shortall, S E ^a   Fone, K C F ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

5 hydroxytryptamine; body temperature; cathinones; dopamine; drug metabolism; locomotion; MDMA; mephedrone

Indexed keywords

3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4' METHYLMETHCATHINONE; CARRIER PROTEIN; CATHINONE; DOPAMINE; DOPAMINE TRANSPORTER; DRUG METABOLITE; MONOAMINE; MONOAMINE RECEPTOR; MONOAMINE TRANSPORTER; RECEPTOR; SEROTONIN; SEROTONIN TRANSPORTER; UNCLASSIFIED DRUG; BIOGENIC AMINE; METHAMPHETAMINE; STREET DRUG;

BEHAVIOR DISORDER; BINDING AFFINITY; BRAIN LEVEL; CARDIOVASCULAR EFFECT; CARDIOVASCULAR FUNCTION; CHEMICAL STRUCTURE; DOPAMINE RELEASE; DRUG EFFECT; DRUG METABOLISM; DRUG SELF ADMINISTRATION; EXPERIMENTAL ANIMAL; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LOCOMOTION; METHAMPHETAMINE DEPENDENCE; NEUROTOXICITY; NONHUMAN; PHARMACOKINETICS; PLASMA HALF LIFE; PRIORITY JOURNAL; RECTUM TEMPERATURE; REVIEW; RODENT; SEROTONIN RELEASE; THERMODYNAMICS; ANALOGS AND DERIVATIVES; ANIMAL; BRAIN; CHEMISTRY; DRUG EFFECTS; DRUG SCREENING; METABOLISM; MOTOR ACTIVITY; MOUSE; PHYSIOLOGY; PROCEDURES; RAT;

ANIMALS; BIOGENIC MONOAMINES; BRAIN; DRUG EVALUATION, PRECLINICAL; HUMANS; METHAMPHETAMINE; MICE; MOTOR ACTIVITY; N-METHYL-3,4-METHYLENEDIOXYAMPHETAMINE; RATS; STREET DRUGS;

EID: 84898636024     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12628     Document Type: Review

References (147)

1. Aarde SM, Angrish D, Barlow DJ, Wright Jr MJ, Vandewater SA, Creehan KM, et al. (2013). Mephedrone (4-methylmethcathinone) supports intravenous self-administration in Sprague-Dawley and Wistar rats. Addict Biol 18: 786-799.
2. Aberg M, Wade D, Wall E, Izenwasser S, (2007). Effect of MDMA (ecstasy) on activity and cocaine conditioned place preference in adult and adolescent rats. Neurotoxicol Teratol 29: 37-46. (Pubitemid 46205157)
3. ACMD (2010). Consideration of the cathinones. Home office report. Available at: http://www.homeoffice.gov.uk/publications/agencies-public-bodies/ acmd1/acmd-cathinodes-report-2010?view=Standard&pubID=878838 (accessed 21/3/2014).
4. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, Peters JA, Harmar AJ, and CGTP Collaborators (2013) the Concise Guide to PHARMACOLOGY 2013/14: G-Protein Coupled Receptors. Br J Pharmacol 170: 1459-1581.
5. Al-Sahli W, Ahmad H, Kheradmand F, Connolly C, Docherty JR, (2001). Effects of methylenedioxymethamphetamine on noradrenaline-evoked contractions of rat right ventricle and small mesenteric artery. Eur J Pharmacol 422: 169-174. (Pubitemid 32595588)
6. Angoa-Pérez M, Kane MJ, Francescutti DM, Sykes KE, Shah MM, Mohammed AM, et al. (2012). Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum. J Neurochem 120: 1097-1107.
7. Angoa-Pérez M, Kane MJ, Briggs DI, Francescutti DM, Sykes CE, Shah MM, et al. (2013). Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA. J Neurochem 125: 102-110.
8. Angoa-Pérez M, Kane MJ, Herrera-Mundo N, Francescutti DM, Kuhn DM, (2014). Effects of combined treatment with mephedrone and methamphetamine or 3,4-methylenedioxymethamphetamine on serotonin nerve endings of the hippocampus. Life Sci 97: 31-36.
9. Armstrong BD, Noguchi KK, (2004) the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: an in-vitro autoradiographic study in rats. Neurotoxicology 25: 905-914. (Pubitemid 39335583)
10. Badon LA, Hicks A, Lord K, Ogden BA, Meleg-Smith S, Varner KJ, (2002). Changes in cardiovascular responsiveness and cardiotoxicity elicited during binge administration of ecstasy. J Pharmacol Exp Ther 302: 898-907. (Pubitemid 34920209)
11. Baumann MH, Wang X, Rothman RB, (2007). 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings. Psychopharmacology (Berl) 189: 407-424. (Pubitemid 44791212)
12. Baumann MH, Zolkowska D, Kim I, Scheidweiler KB, Rothman RB, Huestis MA, (2009). Effects of dose and route of administration on pharmacokinetics of (±)-3,4-methylenedioxymethamphetamine (MDMA) in the rat. Drug Metab Dispos 37: 2163-2170.
13. Baumann MH, Ayestas MA, Partilla JS, Sink JR, Shulgin AT, Daley PF, et al. (2011) the designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37: 1192-1203.
14. Baumann MH, Partilla JS, Lehner KR, (2013a). Psychoactive 'bath salts': not so soothing. Eur J Pharmacol 698: 1-5.
15. Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, et al. (2013b). Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products. Neuropsychopharmacology 38: 552-562.
16. Benturquia N, Courtin C, Noble F, Marie-Claire C, (2008). Involvement of D1 dopamine receptor in MDMA-induced locomotor activity and striatal gene expression in mice. Brain Res 1211: 1-5.
17. Bexis S, Docherty JR, (2006). Effects of MDMA, MDA and MDEA on blood pressure, heart rate, locomotor activity and body temperature in the rat involve α-adrenoceptors. Br J Pharmacol 147: 926-934.
18. Bird J, Schenk S, (2013). Contribution of impulsivity and novelty seeking to the acquisition and maintenance of MDMA self-administration. Addict Biol 18: 654-664.
19. 2-like agonists. Psychopharmacology (Berl) 223: 389-399.
20. Brandt SD, Sumnall HR, Measham F, Cole J, (2010). Analyses of second-generation 'legal highs' in the UK: initial findings. Drug Test Anal 2: 377-382.
21. Brunt TM, Poortman A, Niesink RJM, van den Brink W, (2011). Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol 25: 1543-1547.
22. Cadet JL, Krasnova IN, Jayanthi S, Lyles J, (2007). Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 11: 183-202.
23. Cameron K, Kolanos R, Verkariya R, De Felice L, Glennon RA, (2013). Mephedrone and methylenedioxypyrovalerone (MDPV), major constituents of 'bath salts,' produce opposite effects at the human dopamine transporter. Psychopharmacology (Berl) 227: 493-499.
24. Capela JP, Meisel A, Abreu AR, Branco PS, Ferreira LM, Lobo AM, et al. (2006). Neurotoxicity of ecstasy metabolites in rat cortical neurons, and influence of hyperthermia. J Pharmacol Exp Ther 316: 53-61. (Pubitemid 41832580)
25. Capela JP, Carmo H, Remiao F, Bastos ML, Meisel A, Carvalho F, (2009). Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39: 210-271.
26. Carhart-Harris RL, King LA, Nutt DJ, (2011). A web-based survey on mephedrone. Drug Alcohol Depend 118: 19-22.
27. Carson DS, Hunt GE, Guastella AJ, Barber L, Cornish JL, Arnold JC, et al. (2010). Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus. Addict Biol 15: 448-463.
28. Colado MI, Green AR, (1994). A study of the mechanism of MDMA ('ecstasy')-induced neurotoxicity of 5-HT neurones using chlormethiazole, dizocilpine and other protective compounds. Br J Pharmacol 111: 131-136. (Pubitemid 24148716)
29. Colado MI, Green AR, (1995) the spin trap reagent α-phenyl-N-tert- butyl nitrone prevents 'ecstasy'-induced neurodegeneration of 5-hydroxytryptamine neurons. Eur J Pharmacol 280: 343-346.
30. Colado MI, Murray TK, Green AR, (1993). 5-HT loss in rat brain following 3,4 methylenedioxymethamphetamine, p-chloroamphetamine and fenfluramine administration and effects of chlormethiazole and dizocilpine. Br J Pharmacol 108: 583-589. (Pubitemid 23067921)
31. Cole JC, Sumnall HR, (2003). Altered states: the clinical effects of 'ecstasy'. Pharmacol Ther 98: 35-58. (Pubitemid 36355889)
32. Colussi-Mas J, Wise RJ, Howard A, Schenk S, (2010). Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine. Int J Neuropsychopharmacol 13: 1315-1327.
33. Cornish JL, Shahnawaz Z, Thompson MR, Wong S, Morley KC, Hunt GE, et al. (2003). Heat increases 3,4-methylenedioxymethamphetamine self-administration and social effects in rats. Eur J Pharmacol 482: 339-341. (Pubitemid 37505963)
34. Costa E, Green AR, Koslow SH, LeFevre HF, Revuelta AV, Wang C, (1972). Dopamine and norepinephrine in noradrenergic axons: a study in vivo of their precursor product relationship by mass fragmentography and radiochemistry. Pharmacol Rev 24: 167-190.
35. Dal Cason TA, Young R, Glennon RA, (1997). Cathinone: an investigation of several N-alkyl and methylenedioxy-substituted analogs. Pharmacol Biochem Behav 58: 1109-1116. (Pubitemid 28108223)
36. Dargan PI, Albert S, Wood DM, (2010). Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change. QJM 103: 875-879.
37. Dargan PI, Sedefov R, Gallegos A, Wood DM, (2011) the pharmacology and toxicology of the synthetic cathinone mephedrone (4-methylmethcathinone). Drug Test Anal 3: 454-463.
38. Davey Z, Corazza O, Schifano F, Deluca P, (2010). Mass-information: mephedrone, myths, and the new generation of legal highs. Drugs Alcohol Today 10: 24-28.
39. De La Garza R 2nd, Fabrizio KR, Gupta A, (2007). Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns. Psychopharmacology (Berl) 189: 425-434. (Pubitemid 44791213)
40. Docherty JR, Green AR, (2010) the role of monoamines in the changes in body temperature induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and its derivatives. Br J Pharmacol 160: 1029-1044.
41. Dowling GP, McDonough ET, Bost RO, (1987). 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA. J Am Med Assoc 257: 1615-1617. (Pubitemid 17031815)
42. Dybdal-Hargreaves NF, Holder ND, Ottoson PE, Sweeney MD, Williams T, (2013). Mephedrone: public health risk, mechanisms of action, and behavioral effects. Eur J Pharmacol 714: 32-40.
43. Dyer C, (2010). Mephedrone is an amphetamine 'by another name,' drug adviser tells MPs. BMJ 340: c1690.
44. EMCDDA (2010). Annual report 2010: the state of the drugs problem in Europe. Available at: http://www.emcdda.europa.eu/publications/annual-report/ 2010 (accessed 21/3/2014).
45. EMCDDA (2011). Report on the risk assessment of mephedrone in the framework of the Council Decision on new psychoactive substances. Available at: http://www.emcdda.europa.eu/html.cfm/index116639EN.html (accessed 21/3/2014).
46. EROWID (2013). Doses. Available at: http://www.erowid.org/chemicals/4- methylmethcathinone/4-methylmethcathinone-dose.shtml (Accessed 21/3/2014).
47. Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A, (2013). Substituted methcathinones differ in receptor and transported interactions. Biochem Pharmacol 85: 1803-1815.
48. Fantegrossi WE, Kiessel CL, De la Garza R 2nd, Woods JH, (2005). Serotonin synthesis inhibition reveals distinct mechanisms of action for MDMA and its enantiomers in the mouse. Psychopharmacology (Berl) 181: 529-536. (Pubitemid 41480902)
49. Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR, (2007). New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 47: 681-698.
50. Garrett G, Sweeney M, (2010) the serotonin syndrome as a result of mephedrone toxicity. BMJ Case Rep. doi: 10.1136/bcr.042010.2925
51. Green AR, Grahame-Smith DG, (1976). Effects of drugs on the processes regulating the functional activity of brain 5-hydroxytryptamine. Nature 260: 487-491.
52. Green AR, Mechan AO, Elliott JM, O'Shea E, Colado MI, (2003) the pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). Pharmacol Rev 55: 463-508. (Pubitemid 37013213)
53. Green AR, O'Shea E, Saadat KS, Elliott JM, Colado MI, (2005). Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed at different ambient room temperatures. Br J Pharmacol 146: 306-312. (Pubitemid 43079971)
54. Green AR, King MV, Shortall SE, Fone KC, (2012a). Lost in translation: preclinical studies on MDMA provide information on mechanisms of action, but do not allow accurate prediction of adverse events in humans. Br J Pharmacol 166: 1523-1536.
55. Green AR, King MV, Shortall SE, Fone KC, (2012b). Ecstasy cannot be assumed to be 3,4-methylenedioxyamphetamine (MDMA). Br J Pharmacol 166: 1521-1522.
56. Gregg RA, Tallarida CS, Reitz A, McCurdy C, Rawls SM, (2013). Mephedrone (4-methylmethcathinone), a principal constituent of psychoactive bath salts, produces behavioral sensitization in rats. Drug Alcohol Depend 133: 746-750.
57. Hadlock GC, Webb KM, McFadden LM, Chu PW, Ellis JD, Allen SC, et al. (2011). 4-Methylmethcathinone (mephedrone): neuropharmacological effects of a designer stimulant of abuse. J Pharmacol Exp Ther 339: 530-536.
58. Haggin P, (2012). Obama signs federal ban on 'bath salt' drugs. TIME online. Available at: http://newsfeed.time.com/2012/07/10/obama-signs-federal- ban-on-bath-salt-drugs (accessed 17/9/2013).
59. Halpern P, Moskovich J, Avrahami B, Bentur Y, Soffer D, Peleg K, (2011). Morbidity associated with MDMA (ecstasy) abuse: a survey of emergency department admissions. Hum Exp Toxicol 30: 259-266.
60. Hargreaves GA, Hunt GE, Cornish JL, McGregor IS, (2007). High ambient temperature increases 3,4- methylenedioxymethamphetamine (MDMA, 'ecstasy')-induced Fos expression in a region-specific manner. Neuroscience 145: 764-774. (Pubitemid 46341666)
61. Henry JA, Jeffreys KJ, Dawling S, (1992). Toxicity and deaths from 3,4 methylenedioxymethamphetamine ('ecstasy'). Lancet 340: 384-387.
62. Ho YJ, Pawlak CR, Guo L, Schwarting RK, (2004). Acute and long-term consequences of single MDMA administration in relation to individual anxiety levels in the rat. Behav Brain Res 149: 135-144. (Pubitemid 38199929)
63. den Hollander B, Rozov S, Linden AM, Uusi-Oukari M, Ojanperä I, Korpi ER, (2013). Long-term cognitive and neurochemical effects of 'bath salt' designer drugs methylone and mephedrone. Pharmacol Biochem Behav 103: 501-509.
64. Hotchkiss AJ, Gibb JW, (1980). Long-term effects of multiple doses of methamphetamine on tryptophan hydroxylase and tyrosine hydroxylase activity in rat brain. J Pharmacol Exp Ther 214: 257-262. (Pubitemid 10049032)
65. Huang PK, Aarde SM, Angrish D, Houseknecht KL, Dickerson TJ, Taffe MA, (2012). Contrasting effects of d-methamphetamine, 3,4- methylenedioxymethamphetamine, 3,4-methylenedioxypyrovalerone, and 4-methylmethcathinone on wheel activity in rats. Drug Alcohol Depend 126: 168-175.
66. 2-adrenergic agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4- methylenedioxymethamphetamine in healthy volunteers. J Pharmacol Exp Ther 340: 286-294.
67. Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R, et al. (2012b) the norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA ('ecstasy') in humans. Clin Pharmacol Ther 90: 246-255.
68. Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krähenbühl S, et al. (2012c). Duloxetine inhibits effects of MDMA ('ecstasy') in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS ONE 7: e36476.
69. James D, Adams RD, Spears R, Cooper G, Lupton DJ, Thompson JP, et al. (2011). Clinical characteristics of mephedrone toxicity reported to the U.K. National Poisons Information Service. Emerg Med J 28: 686-689.
70. Johnson EA, O'Callaghan JP, Miller DB, (2002a). Chronic treatment with supraphysiological levels of corticosterone enhances D-MDMA-induced dopaminergic neurotoxicity in the C57BL/6J female mouse. Brain Res 933: 130-138. (Pubitemid 34270616)
71. Johnson EA, Shvedova AA, Kisin E, O'Callaghan JP, Kommineni C, Miller DB, (2002b). d-MDMA during vitamin E deficiency: effects on dopaminergic neurotoxicity and hepatotoxicity. Brain Res 933: 150-163. (Pubitemid 34270619)
72. Joksovic P, Mellos N, van Wattum PJ, Chiles C, (2012). 'Bath salts'-induced psychosis and serotonin toxicity. J Clin Psychiatry 73: 1125.
73. Jones S, Fileccia EL, Murphy M, Fowler MJ, King MV, Shortall SE, et al. (2014). Cathinone increases body temperature, enhances locomotor activity, and induces striatal c-fos expression in the Siberian hamster. Neurosci Lett 559: 34-38.
74. Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, et al. (2011). Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. Br J Pharmacol 164: 1949-1958.
75. Kelly JP, (2011). Cathinone derivatives: a review of their chemistry, pharmacology and toxicology. Drug Test Anal 3: 439-453.
76. Kovacs K, (2008). Measurement of immediate-early gene activation-c-fos and beyond. J Neuroendocrinol 20: 665-672. (Pubitemid 351858715)
77. Laws KR, Kokkalis J, (2007). Ecstasy (MDMA) and memory function: a meta-analytic update. Hum Psychopharmacol 22: 381-388. (Pubitemid 47316122)
78. Leonardi ET, Azmitia EC, (1994). MDMA (ecstasy) inhibition of MAO type A and type B; comparisons with fenfluramine and fluoxetine (Prozac). Neuropsychopharmacology 10: 231-238. (Pubitemid 2122736)
79. Lester SJ, Baggott M, Welm S, Schiller NB, Jones RT, Foster E, et al. (2000). Cardiovascular effects of 3,4-methylenedioxymethamphetamine: a double blind, placebo-controlled trial. Ann Intern Med 133: 969-973. (Pubitemid 32003513)
80. Lisek R, Xu W, Yuvasheva E, Chiu YT, Reitz AB, Liu-Chen LY, et al. (2012). Mephedrone ('bath salt') elicits conditioned place preference and dopamine-sensitive motor activation. Drug Alcohol Depend 126: 257-262.
81. Lõpez-Arnau R, Martínez-Clemente J, Pubill D, Escubedo E, Camarasa J, (2012). Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone. Br J Pharmacol 167: 407-420.
82. Logan BJ, Laverty R, Sanderson WD, Yee YB, (1988). Differences between rats and mice in MDMA (methylenedioxymethylamphetamine) neurotoxicity. Eur J Pharmacol 152: 227-234.
83. Martínez-Clemente J, Escubedo E, Pubill D, Camarasa J, (2012). Interaction of mephedrone with dopamine and serotonin targets in rats. Eur Neuropsychopharmacol 22: 231-236.
84. Martínez-Clemente J, Lõpez-Arnau R, Carbõ M, Pubill D, Camarasa J, Escubedo E, (2013). Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics. Psychopharmacology (Berl) 229: 295-306.
85. Marusich JA, Grant KR, Blough BE, Wiley JL, (2012). Effects of synthetic cathinones contained in 'bath salts' on motor behavior and a functional observational battery in mice. Neurotoxicology 33: 1305-1313.
86. Maskell PD, De Paoli G, Seneviratne C, Pounder DJ, (2011). Mephedrone (4-methylmethcathinone)-related deaths. J Anal Toxicol 35: 188-191.
87. Measham F, Moore K, Newcombe R, Smith Z, (2010). Tweaking, bombing, dabbing and stockpiling: the emergence of mephedrone and the perversity of prohibition. Drugs Alcohol Today 10: 14-21.
88. Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, et al. (2012). Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicol Lett 208: 62-68.
89. Meyer MR, Wilhelm J, Peters FT, Maurer HH, (2010). Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry. Anal Bioanal Chem 397: 1225-1233.
90. Miller DB, O'Callaghan JP, (1995) the role of temperature, stress, and other factors in the neurotoxicity of the substituted amphetamines 3,4-methylenedioxymethamphetamine and fenfluramine. Mol Neurobiol 11: 177-192.
91. Miller ML, Creehan KM, Angrish D, Barlow DJ, Houseknecht KL, Dickerson TJ, et al. (2013). Changes in ambient temperature differentially alter the thermoregulatory, cardiac and locomotor stimulant effects of 4-methylmethcathinone (mephedrone). Drug Alcohol Depend 127: 248-253.
92. Moore K, Dargan PI, Wood DM, Measham F, (2013). Do novel psychoactive substances displace established club drugs, supplement them or act as drugs of initiation? The relationship between mephedrone, ecstasy and cocaine. Eur Addict Res 19: 276-282.
93. Morris K, (2010). UK places generic ban on mephedrone drug family. Lancet 375: 1333-1334.
94. Motbey CP, Karanges E, Li KM, Wilkinson S, Winstock AR, Ramsey J, et al. (2012a). Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion. PLoS ONE 7: e45473.
95. Motbey CP, Hunt GE, Bowen MT, Artiss S, McGregor IS, (2012b). Mephedrone (4-methylmethcathinone, 'meow'): acute behavioural effects and distribution of Fos expression in adolescent rats. Addict Biol 17: 409-422.
96. Motbey CP, Clemens K, Apetz N, Winstock AR, Ramsey J, Kong KM, et al. (2013). High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine. J Psychopharmacol 27: 823-836.
97. Nagai F, Nonaka R, Kamimura K, Satoh H, (2007) the effects of non- medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol 559: 132-137. (Pubitemid 46295399)
98. Neff NH, Lin RC, Ngai SH, Costa E, (1969). Turnover rate measurements of brain serotonin in unanesthetized rats. Adv Biochem Psychopharmacol 1: 91-109.
99. O'Cain PA, Hletko SB, Ogden BA, Varner KJ, (2000). Cardiovascular and sympathetic responses and reflex changes elicited by MDMA. Physiol Behav 70: 141-148.
100. O'Shea E, Granados R, Esteban B, Colado MI, Green AR, (1998) the relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA ('ecstasy'). Neuropharmacology 37: 919-926. (Pubitemid 28375758)
101. O'Shea E, Esteban B, Camarero J, Green AR, Colado MI, (2001). Effect of GBR 12909 and fluoxetine on the acute and long term changes induced by MDMA ('ecstasy') on the 5-HT and dopamine concentrations in mouse brain. Neuropharmacology 40: 65-74. (Pubitemid 33779801)
102. O'Shea E, Escobedo I, Orio L, Sanchez V, Navarro M, Green AR, et al. (2005). Elevation of ambient room temperature has differential effects on MDMA-induced 5-HT and dopamine release in striatum and nucleus accumbens of rats. Neuropsychopharmacology 30: 1312-1323. (Pubitemid 40848085)
103. O'Shea E, Orio L, Escobedo I, Sanchez V, Camarero J, Green AR, et al. (2006). MDMA-induced neurotoxicity: long-term effects on 5-HT biosynthesis and the influence of ambient temperature. Br J Pharmacol 148: 778-785. (Pubitemid 44079407)
104. Parrott AC, (2012a). MDMA and temperature: a review of the thermal effects of 'Ecstasy' in humans. Drug Alcohol Depend 121: 1-9.
105. Parrott AC, (2012b). MDMA and 5-HT neurotoxicity: the empirical evidence for its adverse effects in humans-no need for translation. Br J Pharmacol 166: 1518-1520.
106. Parrott AC, (2013). MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational 'Ecstasy' users. Neurosci Biobehav Rev 37: 1466-1484.
107. Pedersen AJ, Reitzel LA, Johansen SS, Linnet K, (2012). In vitro metabolism studies on mephedrone and analysis of forensic cases. Drug Test Anal 5: 430-438.
108. Pedersen NP, Blessing WW, (2001). Cutaneous vasoconstriction contributes to hyperthermia induced by 3,4-methylenedioxymethamphetamine (ecstasy) in conscious rabbits. J Neurosci 21: 8648-8865.
109. Piper BJ, Meyer JS, (2004). Memory deficit and reduced anxiety in young adult rats given repeated intermittent MDMA treatment during the periadolescent period. Pharmacol Biochem Behav 79: 723-731. (Pubitemid 39600612)
110. Prosser JM, Nelson LS, (2012) the toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol 8: 33-42.
111. Rasimas JJ, (2013). 'Bath salts' and the return of the serotonin syndrome. J Clin Psychiatry 73: 1126-1127.
112. Redfern WS, MacLean MR, Clague RU, McGrath JC, (1995) the role of alpha 2-adrenoceptors in the vasculature of the rat tail. Br J Pharmacol 114: 1724-1730.
113. Regan L, Mitchelson M, Macdonald C, (2011). Mephedrone toxicity in a Scottish emergency department. Emerg Med J 28: 1055-1058.
114. Risbrough VB, Masten VL, Caldwell S, Paulus MP, Low MJ, Geyer MA, (2006). Differential contributions of dopamine D1, D2, and D3 receptors to MDMA-induced effects on locomotor behavior patterns in mice. Neuropsychopharmacology 31: 2349-2358. (Pubitemid 44607051)
115. Robinson JE, Agoglia AE, Fish EW, Krouse MC, Malanga CJ, (2012). Mephedrone (4-methylmethcathinone) and intracranial self-stimulation in C57BL/6J mice: comparison to cocaine. Behav Brain Res 234: 76-81.
116. Rockhold RW, Carlton FB Jr, Corkern R, Derouen L, Bennett JG, Hume AS, (1997). Methcathinone intoxication in the rat: abrogation by dextrorphan. Ann Emerg Med 29: 383-391. (Pubitemid 27106697)
117. Rodsiri R, Spicer C, Green AR, Marsden CA, Fone KC, (2011). Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats. Psychopharmacology (Berl) 213: 365-376.
118. Rothman RB, Baumann MH, (2003). Monoamine transporters and psychostimulant drugs. Eur J Pharmacol 479: 23-40. (Pubitemid 37377873)
119. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, et al. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39: 32-41.
120. Sare J, (2011). How the media helped ban mephedrone. Br Med J 342: d1138.
121. Schenk S, (2009). MDMA self-administration in laboratory animals: a summary of the literature and proposal for future research. Neuropsychobiology 60: 130-136.
122. Schifano F, Albanese A, Fergus S, Stair JL, Deluca P, Corazza O, et al. (2011). Mephedrone (4-methylmethcathinone; 'meow meow'): chemical, pharmacological and clinical issues. Psychopharmacology (Berl) 214: 593-602.
123. Schifano F, Corkery J, Ghodse AH, (2012). Suspected and confirmed fatalities associated with mephedrone (4-methylmethcathinone, 'meow meow') in the United Kingdom. J Clin Psychopharmacol 32: 710-714.
124. Shortall SE, Green AR, Swift KM, Fone KC, King MV, (2013a). Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. Br J Pharmacol 168: 966-977.
125. Shortall SE, Byatt S, Kaufman N, Lipman H, Smith G, Green AR, et al. (2013b). Caffeine alters the behavioural and thermoregulatory responses to mephedrone without causing long-term neurotoxicity. J Psychopharmacol 27: A63.
126. Shortall SE, Macerola AE, Swaby RT, Jayson R, Korsah C, Pillidge KE, et al. (2013c). Behavioural and neurochemical comparison of chronic intermittent cathinone, mephedrone and MDMA administration to the rat. Eur Neuropsychopharmacol 23: 1085-1095.
127. Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, et al. (2013). Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168: 458-470.
128. Sitte HH, Freissmuth M, (2010) the reverse operation of Na(+)/Cl(-)-coupled neurotransmitter transporters-why amphetamines take two to tango. J Neurochem 112: 340-355.
129. Song BJ, Moon KH, Upreti VV, Eddington ND, Lee IJ, (2010). Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol 11: 434-443.
130. Tariq M, Islam MW, al-Meshal IA, el-Feraly FS, Ageel AM, (1989). Comparative study of cathinone and amphetamine on brown adipose thermogenesis. Life Sci 44: 951-955. (Pubitemid 19084211)
131. Tucker GT, Lennard MS, Ellis SW, Woods HF, Cho AK, Lin LY, et al. (1994) the demethylenation of methylenedioxymethamphetamine ('ecstasy') by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 47: 1151-1156.
132. Van Amsterdam J, Nutt D, van den Brink W, (2013). Generic legislation of new psychoactive drugs. J Psychopharmacol 27: 317-324.
133. Vanattou-Saïfoudine N, McNamara R, Harkin A, (2012). Caffeine provokes adverse interactions with 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and related psychostimulants: mechanisms and mediators. Br J Pharmacol 167: 946-959.
134. Vanderschuren LJ, Kalivas PW, (2000). Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl) 151: 99-120. (Pubitemid 30646415)
135. Vardakou I, Pistos C, Spiliopoulou CH, (2011). Drugs for youth via Internet and the example of mephedrone. Toxicol Lett 201: 191-195.
136. Varner KJ, Daigle K, Weed PF, Lewis PB, Mahne SE, Sankaranarayanan A, et al. (2013). Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats. Psychopharmacology (Berl) 225: 675-685.
137. Verbaten MN, (2003). Specific memory deficits in ecstasy users? The results of a meta-analysis. Hum Psychopharmacol 18: 281-290. (Pubitemid 36722314)
138. Vollenweider FX, Remensberger S, Hell D, Geyer MA, (1999). Opposite effects of 3,4-methylenedioxymethamphetamine (MDMA) on sensorimotor gating in rats versus healthy humans. Psychopharmacology (Berl) 143: 365-372. (Pubitemid 29222481)
139. Winstock A, Mitcheson L, Ramsey J, Davies S, Puchnarewicz M, Marsden J, (2011a). Mephedrone: use, subjective effects and health risks. Addiction 106: 1991-1996.
140. Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F, (2011b). Mephedrone, new kid for the chop? Addiction 106: 154-161.
141. Wood DM, Dargan PI, (2012). Mephedrone (4-methylmethcathinone): what is new in our understanding of its use and toxicity. Prog Neuropsychopharmacol Biol Psychiatry 39: 227-233.
142. Wood DM, Davies S, Greene SL, Button J, Holt DW, Ramsey J, et al. (2010). Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol (Phila) 48: 924-927.
143. Wood DM, Greene SL, Dargan PI, (2011). Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Emerg Med J 28: 280-282.
144. Wood DM, Hunter L, Measham F, Dargan PI, (2012). Limited use of novel psychoactive substances in South London nightclubs. QJM 105: 959-964.
145. Wright MJ Jr, Angrish D, Aarde SM, Barlow DJ, Buczynski MW, Creehan KM, et al. (2012a). Effect of ambient temperature on the thermoregulatory and locomotor stimulant effects of 4-methylmethcathinone in Wistar and Sprague-Dawley rats. PLoS ONE 7: e44652.
146. Wright MJ Jr, Vandewater SA, Angrish D, Dickerson TJ, Taffe MA, (2012b). Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques. Br J Pharmacol 167: 1342-1352.
147. Zawilska JB, Wojcieszak J, (2013). Designer cathinones-an emerging class of novel recreational drugs. Forensic Sci Int 231: 42-53.