Interactions of Cathinone NPS with Human Transporters and Receptors in Transfected Cells

Abstract

Pharmacological assays carried out in transfected cells have been very useful for describing the mechanism of action of cathinone new psychoactive substances (NPS). These in vitro characterizations provide fast and reliable information on psychoactive substances soon after they emerge for recreational use. Well-investigated comparator compounds, such as methamphetamine, 3,4-methylenedioxymethamphetamine, cocaine, and lysergic acid diethylamide, should always be included in the characterization to enhance the translation of the in vitro data into clinically useful information. We classified cathinone NPS according to their pharmacology at monoamine transporters and receptors. Cathinone NPS are monoamine uptake inhibitors and most induce transporter-mediated monoamine efflux with weak to no activity at pre- or postsynaptic receptors. Cathinones with a nitrogen-containing pyrrolidine ring emerged as NPS that are extremely potent transporter inhibitors but not monoamine releasers. Cathinones exhibit clinically relevant differences in relative potencies at serotonin vs. dopamine transporters. Additionally, cathinone NPS have more dopaminergic vs. serotonergic properties compared with their non-β-keto amphetamine analogs, suggesting more stimulant and reinforcing properties. In conclusion, in vitro pharmacological assays in heterologous expression systems help to predict the psychoactive and toxicological effects of NPS.

Keywords

Cathinones Efflux Heterologous expression systems In vitro New psychoactive substances Pharmacology Transporters Uptake 

References

  1. 1.
    EMCDDA (2015). European Drug Report 2015. Luxembourg: European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)Google Scholar
  2. 2.
    Liechti M (2015) Novel psychoactive substances (designer drugs): overview and pharmacology of modulators of monoamine signaling. Swiss Med Wkly 145:w14043PubMedGoogle Scholar
  3. 3.
    Rickli A, Hoener MC, Liechti ME (2015) Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones. Eur Neuropsychopharmacol 25:365–376CrossRefPubMedGoogle Scholar
  4. 4.
    Simmler L, Buser T, Donzelli M, Schramm Y, Dieu LH, Huwyler J et al (2013) Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168:458–470CrossRefPubMedGoogle Scholar
  5. 5.
    Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160CrossRefPubMedGoogle Scholar
  6. 6.
    Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF et al (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37:1192–1203CrossRefPubMedGoogle Scholar
  7. 7.
    Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M et al (2013) Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive 'bath salts' products. Neuropsychopharmacology 38:552–562CrossRefPubMedGoogle Scholar
  8. 8.
    Iversen L, Gibbons S, Treble R, Setola V, Huang XP, Roth BL (2013) Neurochemical profiles of some novel psychoactive substances. Eur J Pharmacol 700:147–151CrossRefPubMedGoogle Scholar
  9. 9.
    Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS et al (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A 90:2542–2546CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Revel FG, Moreau JL, Gainetdinov RR, Bradaia A, Sotnikova TD, Mory R et al (2011) TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci U S A 108:8485–8490CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tatsumi M, Groshan K, Blakely RD, Richelson E (1997) Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 340:249–258CrossRefPubMedGoogle Scholar
  12. 12.
    Groskreutz D, Schenborn ET (1997) Reporter systems. Methods Mol Biol 63:11–30PubMedGoogle Scholar
  13. 13.
    Chaudhary S, Pak JE, Gruswitz F, Sharma V, Stroud RM (2012) Overexpressing human membrane proteins in stably transfected and clonal human embryonic kidney 293S cells. Nat Protoc 7:453–466CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Henry LK, Field JR, Adkins EM, Parnas ML, Vaughan RA, Zou MF et al (2006) Tyr-95 and Ile-172 in transmembrane segments 1 and 3 of human serotonin transporters interact to establish high affinity recognition of antidepressants. J Biol Chem 281:2012–2023CrossRefPubMedGoogle Scholar
  15. 15.
    Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F (2013) Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chamba A, Holder MJ, Barnes NM, Gordon J (2008) Characterisation of the endogenous human peripheral serotonin transporter SLC6A4 reveals surface expression without N-glycosylation. J Neuroimmunol 204:75–84CrossRefPubMedGoogle Scholar
  17. 17.
    Marazziti D, Mandillo S, Di Pietro C, Golini E, Matteoni R, Tocchini-Valentini GP (2007) GPR37 associates with the dopamine transporter to modulate dopamine uptake and behavioral responses to dopaminergic drugs. Proc Natl Acad Sci U S A 104:9846–9851CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Maguire JJ, Kuc RE, Davenport AP (2012) Radioligand binding assays and their analysis. Methods Mol Biol 897:31–77CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang R, Xie X (2012) Tools for GPCR drug discovery. Acta Pharmacol Sin 33:372–384CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Tate CG (2012) A crystal clear solution for determining G-protein-coupled receptor structures. Trends Biochem Sci 37:343–352CrossRefPubMedGoogle Scholar
  21. 21.
    Burlingham BT, Widlanski TS (2003) An intuitive look at the relationship of K-i and IC50: A more general use for the Dixon plot. J Chem Educ 80:214–218CrossRefGoogle Scholar
  22. 22.
    Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108CrossRefPubMedGoogle Scholar
  23. 23.
    Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG et al (2011) Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem 54:3206–3221CrossRefPubMedGoogle Scholar
  24. 24.
    Mazei-Robison MS, Bowton E, Holy M, Schmudermaier M, Freissmuth M, Sitte HH et al (2008) Anomalous dopamine release associated with a human dopamine transporter coding variant. J Neurosci 28:7040–7046CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Prasad HC, Zhu CB, McCauley JL, Samuvel DJ, Ramamoorthy S, Shelton RC et al (2005) Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. Proc Natl Acad Sci U S A 102:11545–11550CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Prosser RA, Stowie A, Amicarelli M, Nackenoff AG, Blakely RD, Glass JD (2014) Cocaine modulates mammalian circadian clock timing by decreasing serotonin transport in the SCN. Neuroscience 275:184–193CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Thompson BJ, Jessen T, Henry LK, Field JR, Gamble KL, Gresch PJ et al (2011) Transgenic elimination of high-affinity antidepressant and cocaine sensitivity in the presynaptic serotonin transporter. Proc Natl Acad Sci U S A 108:3785–3790CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Mergy MA, Gowrishankar R, Gresch PJ, Gantz SC, Williams J, Davis GL et al (2014) The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants. Proc Natl Acad Sci U S A 111:E4779–E4788CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Barker EL, Blakely RD (1996) Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter. Mol Pharmacol 50:957–965PubMedGoogle Scholar
  30. 30.
    Wilhelm BG, Mandad S, Truckenbrodt S, Krohnert K, Schafer C, Rammner B et al (2014) Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344:1023–1028CrossRefPubMedGoogle Scholar
  31. 31.
    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 39:32–41CrossRefPubMedGoogle Scholar
  32. 32.
    Rothman RB, Lewis B, Dersch C, Xu H, Radesca L, de Costa BR et al (1993) Identification of a GBR12935 homolog, LR1111, which is over 4,000-fold selective for the dopamine transporter, relative to serotonin and norepinephrine transporters. Synapse 14:34–39CrossRefPubMedGoogle Scholar
  33. 33.
    de la Torre R, Farre M, Ortuno J, Mas M, Brenneisen R, Roset PN et al (2000) Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol 49:104–109CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mueller DM, Rentsch KM (2012) Generation of metabolites by an automated online metabolism method using human liver microsomes with subsequent identification by LC-MS(n), and metabolism of 11 cathinones. Anal Bioanal Chem 402:2141–2151CrossRefPubMedGoogle Scholar
  35. 35.
    Rickli A, Kopf S, Hoener MC, Liechti ME (2015) Pharmacological profile of novel psychoactive benzofurans. Br J Pharmacol 172:3412–3425CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Torok M, Huwyler J, Drewe J, Gutmann H, Fricker G (1998) Transport of the beta-lactam antibiotic benzylpenicillin and the dipeptide glycylsarcosine by brain capillary endothelial cells in vitro. Drug Metab Dispos 26:1144–1148PubMedGoogle Scholar
  37. 37.
    Ukairo OT, Ramanujapuram S, Surratt CK (2007) Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter. Brain Res 1131:68–76CrossRefPubMedGoogle Scholar
  38. 38.
    Hilber B, Scholze P, Dorostkar MM, Sandtner W, Holy M, Boehm S et al (2005) Serotonin-transporter mediated efflux: a pharmacological analysis of amphetamines and non-amphetamines. Neuropharmacology 49:811–819CrossRefPubMedGoogle Scholar
  39. 39.
    Khoshbouei H, Wang H, Lechleiter JD, Javitch JA, Galli A (2003) Amphetamine-induced dopamine efflux. A voltage-sensitive and intracellular Na+-dependent mechanism. J Biol Chem 278:12070–12077CrossRefPubMedGoogle Scholar
  40. 40.
    Verrico CD, Miller GM, Madras BK (2007) MDMA (Ecstasy) and human dopamine, norepinephrine, and serotonin transporters: implications for MDMA-induced neurotoxicity and treatment. Psychopharmacology (Berl) 189:489–503CrossRefGoogle Scholar
  41. 41.
    Hysek CM, Simmler LD, Nicola VG, Vischer N, Donzelli M, Krahenbuhl S et al (2012) Duloxetine inhibits effects of MDMA (“Ecstasy”) in vitro and in humans in a randomized placebo-controlled laboratory study. PLoS One 7, e36476CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Scholze P, Zwach J, Kattinger A, Pifl C, Singer EA, Sitte HH (2000) Transporter-mediated release: a superfusion study on human embryonic kidney cells stably expressing the human serotonin transporter. J Pharmacol Exp Ther 293:870–878PubMedGoogle Scholar
  43. 43.
    Pifl C, Drobny H, Reither H, Hornykiewicz O, Singer EA (1995) Mechanism of the dopamine-releasing actions of amphetamine and cocaine: plasmalemmal dopamine transporter versus vesicular monoamine transporter. Mol Pharmacol 47:368–373PubMedGoogle Scholar
  44. 44.
    Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25:411–414CrossRefPubMedGoogle Scholar
  45. 45.
    Johnson RA, Eshleman AJ, Meyers T, Neve KA, Janowsky A (1998) [3H]substrate- and cell-specific effects of uptake inhibitors on human dopamine and serotonin transporter-mediated efflux. Synapse 30:97–106CrossRefPubMedGoogle Scholar
  46. 46.
    Marcusson JO, Backstrom IT, Ross SB (1986) Single-site model of the neuronal 5-hydroxytryptamine uptake and imipramine-binding site. Mol Pharmacol 30:121–128PubMedGoogle Scholar
  47. 47.
    Nelson PJ, Rudnick G (1979) Coupling between platelet 5-hydroxytryptamine and potassium transport. J Biol Chem 254:10084–10089PubMedGoogle Scholar
  48. 48.
    Talvenheimo J, Nelson PJ, Rudnick G (1979) Mechanism of imipramine inhibition of platelet 5-hydroxytryptamine transport. J Biol Chem 254:4631–4635PubMedGoogle Scholar
  49. 49.
    Eshleman AJ, Carmolli M, Cumbay M, Martens CR, Neve KA, Janowsky A (1999) Characteristics of drug interactions with recombinant biogenic amine transporters expressed in the same cell type. J Pharmacol Exp Ther 289:877–885PubMedGoogle Scholar
  50. 50.
    Rothman RB, Ayestas MA, Dersch CM, Baumann MH (1999) Aminorex, fenfluramine, and chlorphentermine are serotonin transporter substrates. Implications for primary pulmonary hypertension. Circulation 100:869–875CrossRefPubMedGoogle Scholar
  51. 51.
    Rickli A, Luethi D, Reinisch J, Buchy D, Hoener MC, Liechti ME (2015) Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology 99:546–553CrossRefPubMedGoogle Scholar
  52. 52.
    Kalueff AV, Olivier JD, Nonkes LJ, Homberg JR (2010) Conserved role for the serotonin transporter gene in rat and mouse neurobehavioral endophenotypes. Neurosci Biobehav Rev 34:373–386CrossRefPubMedGoogle Scholar
  53. 53.
    Viggiano D, Ruocco LA, Sadile AG (2003) Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder. Neurosci Biobehav Rev 27:623–637CrossRefPubMedGoogle Scholar
  54. 54.
    Xu F, Gainetdinov RR, Wetsel WC, Jones SR, Bohn LM, Miller GW et al (2000) Mice lacking the norepinephrine transporter are supersensitive to psychostimulants. Nat Neurosci 3:465–471CrossRefPubMedGoogle Scholar
  55. 55.
    Sora I, Hall FS, Andrews AM, Itokawa M, Li XF, Wei HB et al (2001) Molecular mechanisms of cocaine reward: combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Natl Acad Sci U S A 98:5300–5305CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    O’Neill B, Tilley MR, Han DD, Thirtamara-Rajamani K, Hill ER, Bishop GA et al (2014) Behavior of knock-in mice with a cocaine-insensitive dopamine transporter after virogenetic restoration of cocaine sensitivity in the striatum. Neuropharmacology 79:626–633CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Brown MT, Bellone C, Mameli M, Labouebe G, Bocklisch C, Balland B et al (2010) Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation. PLoS One 5:e15870CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Hysek CM, Simmler LD, Ineichen M, Grouzmann E, Hoener MC, Brenneisen R et al (2011) The norepinephrine transporter inhibitor reboxetine reduces stimulant effects of MDMA (“ecstasy”) in humans. Clin Pharmacol Ther 90:246–255CrossRefPubMedGoogle Scholar
  59. 59.
    Hysek CM, Simmler LD, Schillinger N, Meyer N, Schmid Y, Donzelli M et al (2014) Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination. Int J Neuropsychopharmacol 17:371–381CrossRefPubMedGoogle Scholar
  60. 60.
    Liechti ME, Baumann C, Gamma A, Vollenweider FX (2000) Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) are attenuated by the serotonin uptake inhibitor citalopram. Neuropsychopharmacology 22:513–521CrossRefPubMedGoogle Scholar
  61. 61.
    Schmid Y, Hysek CM, Simmler LD, Crockett MJ, Quednow BB, Liechti ME (2014) Differential effects of MDMA and methylphenidate on social cognition. J Psychopharmacol 28:847–856CrossRefPubMedGoogle Scholar
  62. 62.
    Schmid Y, Rickli A, Schaffner A, Duthaler U, Grouzmann E, Hysek CM et al (2015) Interactions between bupropion and 3,4-methylenedioxymethamphetamine in healthy subjects. J Pharmacol Exp Ther 353:102–111CrossRefPubMedGoogle Scholar
  63. 63.
    Hysek C, Schmid Y, Rickli A, Simmler L, Donzelli M, Grouzmann E et al (2012) Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans. Br J Pharmacol 166:2277–2288CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Hysek CM, Fink AE, Simmler LD, Donzelli M, Grouzmann E, Liechti ME (2013) alpha(1)-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans. J Clin Psychopharmacol 33:658–666CrossRefPubMedGoogle Scholar
  65. 65.
    Hysek CM, Domes G, Liechti ME (2012) MDMA enhances “mind reading” of positive emotions and impairs “mind reading” of negative emotions. Psychopharmacology (Berl) 222:293–302CrossRefGoogle Scholar
  66. 66.
    Howell LL, Wilcox KM (2002) Functional imaging and neurochemical correlates of stimulant self-administration in primates. Psychopharmacology (Berl) 163:352–361CrossRefGoogle Scholar
  67. 67.
    Derungs A, Schietzel S, Meyer MR, Maurer HH, Krahenbuhl S, Liechti ME (2011) Sympathomimetic toxicity in a case of analytically confirmed recreational use of naphyrone (naphthylpyrovalerone). Clin Toxicol (Phila) 49:691–693CrossRefGoogle Scholar
  68. 68.
    Dolder PC, Schmid Y, Haschke M, Rentsch KM, Liechti ME (2015) Pharmacokinetics and concentration-effect relationship of oral LSD in humans. Int J Neuropsychopharmacol 19Google Scholar
  69. 69.
    Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A (2013) Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol 85:1803–1815CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Rosenauer R, Luf A, Holy M, Freissmuth M, Schmid R, Sitte HH (2013) A combined approach using transporter-flux assays and mass spectrometry to examine psychostimulant street drugs of unknown content. ACS Chem Neurosci 4:182–190CrossRefPubMedGoogle Scholar
  71. 71.
    Ross EA, Reisfield GM, Watson MC, Chronister CW, Goldberger BA (2012) Psychoactive “bath salts” intoxication with methylenedioxypyrovalerone. Am J Med 125:854–858CrossRefPubMedGoogle Scholar
  72. 72.
    Borek HA, Holstege CP (2012) Hyperthermia and multiorgan failure after abuse of “bath salts” containing 3,4-methylenedioxypyrovalerone. Ann Emerg Med 60:103–105CrossRefPubMedGoogle Scholar
  73. 73.
    Murray BL, Murphy CM, Beuhler MC (2012) Death following recreational use of designer drug “bath salts” containing 3,4-Methylenedioxypyrovalerone (MDPV). J Med Toxicol 8:69–75CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Simmler LD, Rickli A, Schramm Y, Hoener MC, Liechti ME (2014) Pharmacological profiles of aminoindanes, piperazines, and pipradrol derivatives. Biochem Pharmacol 88:237–244CrossRefPubMedGoogle Scholar
  75. 75.
    Bauer CT, Banks ML, Blough BE, Negus SS (2013) Use of intracranial self-stimulation to evaluate abuse-related and abuse-limiting effects of monoamine releasers in rats. Br J Pharmacol 168:850–862CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Schindler CW, Thorndike EB, Goldberg SR, Lehner KR, Cozzi NV, Brandt SD et al (2015) Reinforcing and neurochemical effects of the “bath salts” constituents 3,4-methylenedioxypyrovalerone (MDPV) and 3,4-methylenedioxy-N-methylcathinone (methylone) in male rats. Psychopharmacology (Berl)Google Scholar
  77. 77.
    Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (2005) Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs. J Pharmacol Exp Ther 313:848–854CrossRefPubMedGoogle Scholar
  78. 78.
    Rothman RB, Baumann MH (2006) Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs. Ann N Y Acad Sci 1074:245–260CrossRefPubMedGoogle Scholar
  79. 79.
    Watterson LR, Kufahl PR, Nemirovsky NE, Sewalia K, Grabenauer M, Thomas BF et al (2014) Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV). Addict Biol 19:165–174CrossRefPubMedGoogle Scholar
  80. 80.
    Watterson LR, Olive MF (2014) Synthetic cathinones and their rewarding and reinforcing effects in rodents. Adv Neurosci 2014:209875CrossRefGoogle Scholar
  81. 81.
    Sulzer D, Sonders MS, Poulsen NW, Galli A (2005) Mechanisms of neurotransmitter release by amphetamines: a review. Prog Neurobiol 75:406–433CrossRefPubMedGoogle Scholar
  82. 82.
    Rudnick G, Wall SC (1992) The molecular mechanism of “ecstasy” [3,4-methylenedioxy-methamphetamine (MDMA)]: serotonin transporters are targets for MDMA-induced serotonin release. Proc Natl Acad Sci U S A 89:1817–1821CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Steinkellner T, Freissmuth M, Sitte HH, Montgomery T (2011) The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ‘Ecstasy’), methamphetamine and D-amphetamine. Biol Chem 392:103–115CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Hill SL, Thomas SH (2011) Clinical toxicology of newer recreational drugs. Clin Toxicol (Phila) 49:705–719CrossRefGoogle Scholar
  85. 85.
    Nichols DE (2004) Hallucinogens. Pharmacol Ther 101:131–181CrossRefPubMedGoogle Scholar
  86. 86.
    Eshleman AJ, Forster MJ, Wolfrum KM, Johnson RA, Janowsky A, Gatch MB (2014) Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function. Psychopharmacology (Berl) 231:875–888CrossRefGoogle Scholar
  87. 87.
    Caine SB, Thomsen M, Gabriel KI, Berkowitz JS, Gold LH, Koob GF et al (2007) Lack of self-administration of cocaine in dopamine D1 receptor knock-out mice. J Neurosci 27:13140–13150CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Simmler LD, Buchy D, Chaboz S, Hoener MC, Liechti ME (2016) In vitro characterization of psychoactive substances at rat, mouse, and human trace amine-associated receptor 1. J Pharmacol Exp Ther. doi:10.1124/jpet.115.229765 PubMedGoogle Scholar
  89. 89.
    Jing L, Li JX (2015) Trace amine-associated receptor 1: A promising target for the treatment of psychostimulant addiction. Eur J Pharmacol 761:345–352CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Achat-Mendes C, Lynch LJ, Sullivan KA, Vallender EJ, Miller GM (2012) Augmentation of methamphetamine-induced behaviors in transgenic mice lacking the trace amine-associated receptor 1. Pharmacol Biochem Behav 101:201–207CrossRefPubMedGoogle Scholar
  91. 91.
    Di Cara B, Maggio R, Aloisi G, Rivet JM, Lundius EG, Yoshitake T et al (2011) Genetic deletion of trace amine 1 receptors reveals their role in auto-inhibiting the actions of ecstasy (MDMA). J Neurosci 31:16928–16940CrossRefPubMedGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical ResearchUniversity Hospital BaselBaselSwitzerland

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