Advertisement

Electrophysiological Actions of Synthetic Cathinones on Monoamine Transporters

  • Ernesto SolisJr.
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 32)

Abstract

Products containing psychoactive synthetic cathinones, such as mephedrone and 3,4-methylenedioxypyrovalerone (MDPV) are prevalent in our society. Synthetic cathinones are structurally similar to methamphetamine, and numerous synthetics have biological activity at dopamine, serotonin, and norepinephrine transporters. Importantly, monoamine transporters co-transport sodium ions along with their substrate, and movement of substrates and ions through the transporter can generate measurable ionic currents. Here we review how electrophysiological information has enabled us to determine how synthetic cathinones affect transporter-mediated currents in cells that express these transporters. Specifically, drugs that act as transporter substrates induce inward depolarizing currents when cells are held near their resting membrane potential, whereas drugs that act as transporter blockers induce apparent outward currents by blocking an inherent inward leak current. We have employed the two-electrode voltage-clamp technique in Xenopus laevis oocytes overexpressing monoamine transporters to determine whether synthetic cathinones found in the so-called bath salts products behave as blockers or substrates. We also examined the structure–activity relationships for synthetic cathinone analogs related to the widely abused compound MDPV, a common constituent in “bath salts” possessing potent actions at the dopamine transporter.

Keywords

Bath salts Dopamine transporter Serotonin transporter Two-electrode voltage-clamp 

Notes

Acknowledgments

I would like to acknowledge Louis J. De Felice and Michael H. Baumann for valuable input in the writing of the chapter. The work described in this chapter was supported by NIH/NIDA R01DA033930 and R01DA033930-S2.

References

  1. 1.
    Spiller HA, Ryan ML, Weston RG, Jansen J (2011) Clinical experience with and analytical confirmation of “bath salts” and “legal highs” (synthetic cathinones) in the United States. Clin Toxicol (Phila) 49:499–505Google Scholar
  2. 2.
    De Felice LJ, Glennon RA, Negus SS (2014) Synthetic cathinones: chemical phylogeny, physiology, and neuropharmacology. Life Sci 97:20–26CrossRefGoogle Scholar
  3. 3.
    Schechter MD, Glennon RA (1985) Cathinone, cocaine and methamphetamine: similarity of behavioral effects. Pharmacol Biochem Behav 22:913–916PubMedGoogle Scholar
  4. 4.
    Iversen L, White M, Treble R (2014) Designer psychostimulants: pharmacology and differences. Neuropharmacology 87:59–65PubMedGoogle Scholar
  5. 5.
    Saha K, Partilla JS, Lehner KR, Seddik A, Stockner T, Holy M, Sandtner W, Ecker GF, Sitte HH, Baumann MH (2015) ‘Second-generation’ mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function. Neuropsychopharmacology 40:1321–1331PubMedPubMedCentralGoogle Scholar
  6. 6.
    Hoffman BJ, Hansson SR, Mezey E, Palkovits M (1998) Localization and dynamic regulation of biogenic amine transporters in the mammalian central nervous system. Front Neuroendocrinol 19:187–231PubMedGoogle Scholar
  7. 7.
    Tao-Cheng JH, Zhou FC (1999) Differential polarization of serotonin transporters in axons versus soma-dendrites: an immunogold electron microscopy study. Neuroscience 94:821–830PubMedGoogle Scholar
  8. 8.
    Wimalasena K (2011) Vesicular monoamine transporters: structure-function, pharmacology, and medicinal chemistry. Med Res Rev 31:483–519PubMedGoogle Scholar
  9. 9.
    Schloss P, Williams DC (1998) The serotonin transporter: a primary target for antidepressant drugs. J Psychopharmacol 12:115–121PubMedGoogle Scholar
  10. 10.
    Stahl SM (1998) Basic psychopharmacology of antidepressants, part 1: antidepressants have seven distinct mechanisms of action. J Clin Psychiatry 59(Suppl 4):5–14PubMedGoogle Scholar
  11. 11.
    Coppen A, Shaw DM, Herzberg B, Maggs R (1967) Tryptophan in the treatment of depression. Lancet 2:1178–1180PubMedGoogle Scholar
  12. 12.
    Feighner JP (1994) Clinical effects of serotonin reuptake inhibitors--a review. Fortschr Neurol Psychiatr 62(Suppl 1):9–15PubMedGoogle Scholar
  13. 13.
    Vaswani M, Kalra H (2004) Selective serotonin re-uptake inhibitors in anorexia nervosa. Expert Opin Investig Drugs 13:349–357PubMedGoogle Scholar
  14. 14.
    Vaswani M, Linda FK, Ramesh S (2003) Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 27:85–102PubMedGoogle Scholar
  15. 15.
    Barbeau A (1970) Dopamine and disease. Can Med Assoc J 103:824–832PubMedPubMedCentralGoogle Scholar
  16. 16.
    Gainetdinov RR (2008) Dopamine transporter mutant mice in experimental neuropharmacology. Naunyn Schmiedebergs Arch Pharmacol 377:301–313PubMedGoogle Scholar
  17. 17.
    Gainetdinov RR, Caron MG (2003) Monoamine transporters: from genes to behavior. Annu Rev Pharmacol Toxicol 43:261–284PubMedGoogle Scholar
  18. 18.
    Javitch JA, Snyder SH (1984) Uptake of MPP(+) by dopamine neurons explains selectivity of parkinsonism-inducing neurotoxin, MPTP. Eur J Pharmacol 106:455–456PubMedGoogle Scholar
  19. 19.
    Foote SL, Aston-Jones G, Bloom FE (1980) Impulse activity of locus coeruleus neurons in awake rats and monkeys is a function of sensory stimulation and arousal. Proc Natl Acad Sci U S A 77:3033–3037PubMedPubMedCentralGoogle Scholar
  20. 20.
    Schwartz JW, Piston D, DeFelice LJ (2006) Molecular microfluorometry: converting arbitrary fluorescence units into absolute molecular concentrations to study binding kinetics and stoichiometry in transporters. Handb Exp Pharmacol (175):23–57Google Scholar
  21. 21.
    Banks ML, Worst TJ, Rusyniak DE, Sprague JE (2014) Synthetic cathinones (“bath salts”). J Emerg Med 46:632–642PubMedPubMedCentralGoogle Scholar
  22. 22.
    German CL, Fleckenstein AE, Hanson GR (2014) Bath salts and synthetic cathinones: an emerging designer drug phenomenon. Life Sci 97:2–8PubMedPubMedCentralGoogle Scholar
  23. 23.
    Miotto K, Striebel J, Cho AK, Wang C (2013) Clinical and pharmacological aspects of bath salt use: a review of the literature and case reports. Drug Alcohol Depend 132:1–12PubMedGoogle Scholar
  24. 24.
    Valente MJ, Guedes de Pinho P, de Lourdes Bastos M, Carvalho F, Carvalho M (2014) Khat and synthetic cathinones: a review. Arch Toxicol 88:15–45PubMedGoogle Scholar
  25. 25.
    White KJ, Walline CC, Barker EL (2005) Serotonin transporters: implications for antidepressant drug development. AAPS J 7:E421–E433PubMedPubMedCentralGoogle Scholar
  26. 26.
    Sghendo L, Mifsud J (2012) Understanding the molecular pharmacology of the serotonergic system: using fluoxetine as a model. J Pharm Pharmacol 64:317–325PubMedGoogle Scholar
  27. 27.
    Stahl SM (1998) Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord 51:215–235PubMedGoogle Scholar
  28. 28.
    Johansen PO, Krebs TS (2009) How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale. J Psychopharmacol 23:389–391PubMedGoogle Scholar
  29. 29.
    Mithoefer MC, Wagner MT, Mithoefer AT, Jerome L, Doblin R (2011) The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol 25:439–452PubMedPubMedCentralGoogle Scholar
  30. 30.
    Wall SC, Gu H, Rudnick G (1995) Biogenic amine flux mediated by cloned transporters stably expressed in cultured cell lines: amphetamine specificity for inhibition and efflux. Mol Pharmacol 47:544–550PubMedPubMedCentralGoogle Scholar
  31. 31.
    Wu X, Gu HH (1999) Molecular cloning of the mouse dopamine transporter and pharmacological comparison with the human homologue. Gene 233:163–170PubMedGoogle Scholar
  32. 32.
    Henry LK, Blakely RD (2008) Distinctions between dopamine transporter antagonists could be just around the bend. Mol Pharmacol 73:616–618PubMedGoogle Scholar
  33. 33.
    Fleckenstein AE, Volz TJ, Riddle EL, Gibb JW, Hanson GR (2007) New insights into the mechanism of action of amphetamines. Annu Rev Pharmacol Toxicol 47:681–698PubMedPubMedCentralGoogle Scholar
  34. 34.
    Burnette WB, Bailey MD, Kukoyi S, Blakely RD, Trowbridge CG, Justice JB Jr (1996) Human norepinephrine transporter kinetics using rotating disk electrode voltammetry. Anal Chem 68:2932–2938PubMedGoogle Scholar
  35. 35.
    Holmes JC, Rutledge CO (1976) Effects of the d- and l-isomers of amphetamine on uptake, release and catabolism of norepinephrine, dopamine and 5-hydroxytryptamine in several regions of rat brain. Biochem Pharmacol 25:447–451PubMedGoogle Scholar
  36. 36.
    Kuczenski R, Segal DS, Cho AK, Melega W (1995) Hippocampus norepinephrine, caudate dopamine and serotonin, and behavioral responses to the stereoisomers of amphetamine and methamphetamine. J Neurosci 15:1308–1317PubMedGoogle Scholar
  37. 37.
    Phillips AG, Brooke SM, Fibiger HC (1975) Effects of amphetamine isomers and neuroleptics on self-stimulation from the nucleus accumbens and dorsal noradrenergic bundle. Brain Res 85:13–22PubMedGoogle Scholar
  38. 38.
    Cody JT, Valtier S, Nelson SL (2003) Amphetamine enantiomer excretion profile following administration of Adderall. J Anal Toxicol 27:485–492PubMedGoogle Scholar
  39. 39.
    Heal DJ, Cheetham SC, Smith SL (2009) The neuropharmacology of ADHD drugs in vivo: insights on efficacy and safety. Neuropharmacology 57:608–618PubMedGoogle Scholar
  40. 40.
    Najib J (2009) The efficacy and safety profile of lisdexamfetamine dimesylate, a prodrug of d-amphetamine, for the treatment of attention-deficit/hyperactivity disorder in children and adults. Clin Ther 31:142–176PubMedGoogle Scholar
  41. 41.
    Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P 3rd, Everhart ET, Jones RT (2006) Human pharmacology of the methamphetamine stereoisomers. Clin Pharmacol Ther 80:403–420PubMedGoogle Scholar
  42. 42.
    Potkin SG, Karoum F, Chuang LW, Cannon-Spoor HE, Phillips I, Wyatt RJ (1979) Phenylethylamine in paranoid chronic schizophrenia. Science 206:470–471PubMedGoogle Scholar
  43. 43.
    Romanelli F, Smith KM (2006) Clinical effects and management of methamphetamine abuse. Pharmacotherapy 26:1148–1156PubMedGoogle Scholar
  44. 44.
    Winslow BT, Voorhees KI, Pehl KA (2007) Methamphetamine abuse. Am Fam Physician 76:1169–1174PubMedGoogle Scholar
  45. 45.
    Mazei-Robinson MS, Blakely RD (2006) ADHD and the dopamine transporter: are there reasons to pay attention? Handb Exp Pharmacol (175):373–415Google Scholar
  46. 46.
    Arias HR (2009) Is the inhibition of nicotinic acetylcholine receptors by bupropion involved in its clinical actions? Int J Biochem Cell Biol 41:2098–2108PubMedGoogle Scholar
  47. 47.
    De Felice LJ (2016) Chloride requirement for monoamine transporters. Pflugers Arch 468:503–511PubMedPubMedCentralGoogle Scholar
  48. 48.
    Singh SK (2008) LeuT: A prokaryotic stepping stone on the way to a eukaryotic neurotransmitter transporter structure. Channels (Austin) 2Google Scholar
  49. 49.
    Ramamoorthy S, Bauman AL, Moore KR, Han H, Yang-Feng T, Chang AS, Ganapathy V, Blakely RD (1993) Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization. Proc Natl Acad Sci U S A 90:2542–2546PubMedPubMedCentralGoogle Scholar
  50. 50.
    DeFelice LJ, Blakely RD (1996) Pore models for transporters? Biophys J 70:579–580PubMedPubMedCentralGoogle Scholar
  51. 51.
    Galli A, Blakely RD, DeFelice LJ (1996) Norepinephrine transporters have channel modes of conduction. Proc Natl Acad Sci U S A 93:8671–8676PubMedPubMedCentralGoogle Scholar
  52. 52.
    Rudnick G (1998) Bioenergetics of neurotransmitter transport. J Bioenerg Biomembr 30:173–185PubMedGoogle Scholar
  53. 53.
    Rudnick G (1998) Ion-coupled neurotransmitter transport: thermodynamic vs. kinetic determinations of stoichiometry. Methods Enzymol 296:233–247PubMedGoogle Scholar
  54. 54.
    Naftalin RJ (1984) The thermostatics and thermodynamics of cotransport. Biochim Biophys Acta 778:155–175PubMedGoogle Scholar
  55. 55.
    Stein WD, Lieb WR (1986) Transport and diffusion across cell membranes. Academic, OrlandoGoogle Scholar
  56. 56.
    Abramson J, Smirnova I, Kasho V, Verner G, Iwata S, Kaback HR (2003) The lactose permease of Escherichia coli: overall structure, the sugar-binding site and the alternating access model for transport. FEBS Lett 555:96–101PubMedGoogle Scholar
  57. 57.
    Abramson J, Smirnova I, Kasho V, Verner G, Kaback HR, Iwata S (2003) Structure and mechanism of the lactose permease of Escherichia coli. Science 301:610–615PubMedGoogle Scholar
  58. 58.
    Penmatsa A, Wang KH, Gouaux E (2015) X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat Struct Mol Biol 22:506–508PubMedPubMedCentralGoogle Scholar
  59. 59.
    Wang KH, Penmatsa A, Gouaux E (2015) Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature 521:322–327PubMedPubMedCentralGoogle Scholar
  60. 60.
    Yamashita A, Singh SK, Kawate T, Jin Y, Gouaux E (2005) Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature 437:215–223Google Scholar
  61. 61.
    Yernool D, Boudker O, Jin Y, Gouaux E (2004) Structure of a glutamate transporter homologue from Pyrococcus horikoshii. Nature 431:811–818PubMedGoogle Scholar
  62. 62.
    Gu H, Wall SC, Rudnick G (1994) Stable expression of biogenic amine transporters reveals differences in inhibitor sensitivity, kinetics, and ion dependence. J Biol Chem 269:7124–7130PubMedGoogle Scholar
  63. 63.
    McElvain JS, Schenk JO (1992) A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine. Biochem Pharmacol 43:2189–2199PubMedGoogle Scholar
  64. 64.
    Sonders MS, Zhu SJ, Zahniser NR, Kavanaugh MP, Amara SG (1997) Multiple ionic conductances of the human dopamine transporter: the actions of dopamine and psychostimulants. J Neurosci 17:960–974PubMedGoogle Scholar
  65. 65.
    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 278:12070–12077Google Scholar
  66. 66.
    Kahlig KM, Binda F, Khoshbouei H, Blakely RD, McMahon DG, Javitch JA, Galli A (2005) Amphetamine induces dopamine efflux through a dopamine transporter channel. Proc Natl Acad Sci U S A 102:3495–3500PubMedPubMedCentralGoogle Scholar
  67. 67.
    Seidel S, Singer EA, Just H, Farhan H, Scholze P, Kudlacek O, Holy M, Koppatz K, Krivanek P, Freissmuth M, Sitte HH (2005) Amphetamines take two to tango: an oligomer-based counter-transport model of neurotransmitter transport explores the amphetamine action. Mol Pharmacol 67:140–151Google Scholar
  68. 68.
    Sulzer D, Chen TK, Lau YY, Kristensen H, Rayport S, Ewing A (1995) Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport. J Neurosci 15:4102–4108PubMedGoogle Scholar
  69. 69.
    Sulzer D, Maidment NT, Rayport S (1993) Amphetamine and other weak bases act to promote reverse transport of dopamine in ventral midbrain neurons. J Neurochem 60:527–535PubMedPubMedCentralGoogle Scholar
  70. 70.
    Khoshbouei H, Sen N, Guptaroy B, Johnson L, Lund D, Gnegy ME, Galli A, Javitch JA (2004) N-terminal phosphorylation of the dopamine transporter is required for amphetamine-induced efflux. PLoS Biol 2, E78PubMedPubMedCentralGoogle Scholar
  71. 71.
    Fog JU, Khoshbouei H, Holy M, Owens WA, Vaegter CB, Sen N, Nikandrova Y, Bowton E, McMahon DG, Colbran RJ, Daws LC, Sitte HH, Javitch JA, Galli A, Gether U (2006) Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport. Neuron 51:417–429PubMedGoogle Scholar
  72. 72.
    DeFelice LJ (2004) Going against the flow. Nature 432:279PubMedGoogle Scholar
  73. 73.
    DeFelice LJ, Goswami T (2007) Transporters as channels. Annu Rev Physiol 69:87–112PubMedGoogle Scholar
  74. 74.
    Quick MW (2003) Regulating the conducting states of a mammalian serotonin transporter. Neuron 40:537–549PubMedGoogle Scholar
  75. 75.
    Adams SV, DeFelice LJ (2002) Flux coupling in the human serotonin transporter. Biophys J 83:3268–3282PubMedPubMedCentralGoogle Scholar
  76. 76.
    Adams SV, DeFelice LJ (2003) Ionic currents in the human serotonin transporter reveal inconsistencies in the alternating access hypothesis. Biophys J 85:1548–1559PubMedPubMedCentralGoogle Scholar
  77. 77.
    DeFelice LJ, Galli A (1998) Electrophysiological analysis of transporter function. Adv Pharmacol 42:186–190PubMedGoogle Scholar
  78. 78.
    DeFelice LJ, Galli A (1998) Fluctuation analysis of norepinephrine and serotonin transporter currents. Methods Enzymol 296:578–593PubMedGoogle Scholar
  79. 79.
    Galli A, Blakely RD, DeFelice LJ (1998) Patch-clamp and amperometric recordings from norepinephrine transporters: channel activity and voltage-dependent uptake. Proc Natl Acad Sci U S A 95:13260–13265PubMedPubMedCentralGoogle Scholar
  80. 80.
    Galli A, DeFelice LJ, Duke BJ, Moore KR, Blakely RD (1995) Sodium-dependent norepinephrine-induced currents in norepinephrine-transporter-transfected HEK-293 cells blocked by cocaine and antidepressants. J Exp Biol 198:2197–2212PubMedGoogle Scholar
  81. 81.
    Li C, Zhong H, Wang Y, Wang H, Yang Z, Zheng Y, Liu K, Liu Y (2006) Voltage and ionic regulation of human serotonin transporter in Xenopus oocytes. Clin Exp Pharmacol Physiol 33:1088–1092PubMedGoogle Scholar
  82. 82.
    Mager S, Min C, Henry DJ, Chavkin C, Hoffman BJ, Davidson N, Lester HA (1994) Conducting states of a mammalian serotonin transporter. Neuron 12:845–859PubMedGoogle Scholar
  83. 83.
    Petersen CI, DeFelice LJ (1999) Ionic interactions in the Drosophila serotonin transporter identify it as a serotonin channel. Nat Neurosci 2:605–610PubMedGoogle Scholar
  84. 84.
    Ramsey IS, DeFelice LJ (2002) Serotonin transporter function and pharmacology are sensitive to expression level: evidence for an endogenous regulatory factor. J Biol Chem 277:14475–14482PubMedGoogle Scholar
  85. 85.
    Carvelli L, McDonald PW, Blakely RD, Defelice LJ (2004) Dopamine transporters depolarize neurons by a channel mechanism. Proc Natl Acad Sci U S A 101:16046–16051PubMedPubMedCentralGoogle Scholar
  86. 86.
    Ingram SL, Prasad BM, Amara SG (2002) Dopamine transporter-mediated conductances increase excitability of midbrain dopamine neurons. Nat Neurosci 5:971–978PubMedGoogle Scholar
  87. 87.
    Quick MW (2002) Role of syntaxin 1A on serotonin transporter expression in developing thalamocortical neurons. Int J Dev Neurosci 20:219–224PubMedGoogle Scholar
  88. 88.
    Ryan RM, Mindell JA (2007) The uncoupled chloride conductance of a bacterial glutamate transporter homolog. Nat Struct Mol Biol 14:365–371PubMedGoogle Scholar
  89. 89.
    Sonders MS, Amara SG (1996) Channels in transporters. Curr Opin Neurobiol 6:294–302PubMedGoogle Scholar
  90. 90.
    Bruns D (1998) Serotonin transport in cultured leech neurons. Methods Enzymol 296:593–607PubMedGoogle Scholar
  91. 91.
    Bruns D, Engert F, Lux HD (1993) A fast activating presynaptic reuptake current during serotonergic transmission in identified neurons of Hirudo. Neuron 10:559–572PubMedGoogle Scholar
  92. 92.
    Rodriguez-Menchaca AA, Solis E Jr, Cameron K, De Felice LJ (2012) S(+)amphetamine induces a persistent leak in the human dopamine transporter: molecular stent hypothesis. Br J Pharmacol 165:2749–2757PubMedPubMedCentralGoogle Scholar
  93. 93.
    Wang HW, Li CZ, Yang ZF, Zheng YQ, Zhang Y, Liu YM (2006) Electrophysiological effect of fluoxetine on Xenopus oocytes heterologously expressing human serotonin transporter. Acta Pharmacol Sin 27:289–293PubMedGoogle Scholar
  94. 94.
    Storustovu S, Sanchez C, Porzgen P, Brennum LT, Larsen AK, Pulis M, Ebert B (2004) R-citalopram functionally antagonises escitalopram in vivo and in vitro: evidence for kinetic interaction at the serotonin transporter. Br J Pharmacol 142:172–180PubMedCentralGoogle Scholar
  95. 95.
    Lin F, Lester HA, Mager S (1996) Single-channel currents produced by the serotonin transporter and analysis of a mutation affecting ion permeation. Biophys J 71:3126–3135PubMedPubMedCentralGoogle Scholar
  96. 96.
    Barker EL, Moore KR, Rakhshan F, Blakely RD (1999) Transmembrane domain I contributes to the permeation pathway for serotonin and ions in the serotonin transporter. J Neurosci 19:4705–4717PubMedGoogle Scholar
  97. 97.
    Sandtner W, Schmid D, Schicker K, Gerstbrein K, Koenig X, Mayer FP, Boehm S, Freissmuth M, Sitte HH (2014) A quantitative model of amphetamine action on the 5-HT transporter. Br J Pharmacol 171:1007–1018PubMedPubMedCentralGoogle Scholar
  98. 98.
    De Felice LJ, Cameron KN (2015) Comments on ‘A quantitative model of amphetamine action on the serotonin transporter’, by Sandtner et al., Br J Pharmacol 171: 1007–1018. Br J Pharmacol 172:4772–4774PubMedPubMedCentralGoogle Scholar
  99. 99.
    Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV (2012) The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology 37:1192–1203PubMedPubMedCentralGoogle Scholar
  100. 100.
    Baumann MH, Partilla JS, Lehner KR, Thorndike EB, Hoffman AF, Holy M, Rothman RB, Goldberg SR, Lupica CR, Sitte HH, Brandt SD, Tella SR, Cozzi NV, Schindler CW (2013) Powerful cocaine-like actions of 3,4-methylenedioxypyrovalerone (MDPV), a principal constituent of psychoactive ‘bath salts’ products. Neuropsychopharmacology 38:552–562PubMedPubMedCentralGoogle Scholar
  101. 101.
    Marusich JA, Antonazzo KR, Wiley JL, Blough BE, Partilla JS, Baumann MH (2014) Pharmacology of novel synthetic stimulants structurally related to the “bath salts” constituent 3,4-methylenedioxypyrovalerone (MDPV). Neuropharmacology 87:206–213PubMedPubMedCentralGoogle Scholar
  102. 102.
    Cozzi NV, Brandt SD, Daley PF, Partilla JS, Rothman RB, Tulzer A, Sitte HH, Baumann MH (2013) Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs. Eur J Pharmacol 699:180–187Google Scholar
  103. 103.
    Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A (2013) Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol 85:1803–1815PubMedPubMedCentralGoogle Scholar
  104. 104.
    Simmler LD, Buser TA, Donzelli M, Schramm Y, Dieu LH, Huwyler J, Chaboz S, Hoener MC, Liechti ME (2013) Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol 168:458–470PubMedPubMedCentralGoogle Scholar
  105. 105.
    Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160Google Scholar
  106. 106.
    Cameron KN, Kolanos R, Solis E Jr, Glennon RA, De Felice LJ (2013) Bath salts components mephedrone and methylenedioxypyrovalerone (MDPV) act synergistically at the human dopamine transporter. Br J Pharmacol 168:1750–1757PubMedPubMedCentralGoogle Scholar
  107. 107.
    Kolanos R, Solis E Jr, Sakloth F, De Felice LJ, Glennon RA (2013) “Deconstruction” of the abused synthetic cathinone methylenedioxypyrovalerone (MDPV) and an examination of effects at the human dopamine transporter. ACS Chem Neurosci 4:1524–1529PubMedPubMedCentralGoogle Scholar
  108. 108.
    Bulling S, Schicker K, Zhang YW, Steinkellner T, Stockner T, Gruber CW, Boehm S, Freissmuth M, Rudnick G, Sitte HH, Sandtner W (2012) The mechanistic basis for noncompetitive ibogaine inhibition of serotonin and dopamine transporters. J Biol Chem 287:18524–18534PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Open Access This chapter is licensed under the terms of the Creative Commons Attribution-NonCommercial 2.5 International License (http://creativecommons.org/licenses/by-nc/2.5/), which permits any noncommercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Authors and Affiliations

  1. 1.In Vivo Electrophysiology Unit, Behavioral Neuroscience Research BranchNational Institute on Drug Abuse – Intramural Research Program, National Institutes of Health, Triad Technology CenterBaltimoreUSA

Personalised recommendations