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Acute effects of BZP, TFMPP and the combination of BZP and TFMPP in comparison to dexamphetamine on an auditory oddball task using electroencephalography: a single-dose study

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Abstract

Rationale

Piperazine-based designer drugs such as benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been marketed and sold as legal alternatives to dexamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. When administered in combination, BZP + TFMPP have been reported to produce drug-drug synergism in rodents by stimulating the release of dopamine and serotonin.

Objectives

This study was to evaluate the acute event-related potential effects of BZP, TFMPP or the combination of BZP + TFMPP compared with dexamphetamine in young healthy male adults.

Methods

A double-blind, randomised, placebo-controlled study investigated the effects of BZP, TFMPP, the combination of BZP + TFMPP, and dexamphetamine on the event-related potentials during an auditory oddball task. Healthy, right-handed males were given a single oral dose of either BZP (200 mg), TFMPP (60 mg), a combination of BZP + TFMPP (100/30 mg), dexamphetamine (20 mg) or placebo (lactose) and tested both before and 120 min after drug administration.

Results

A single dose of either TMFPP (t = −2.29, p = 0.03) or dexamphetamine (t = −2.33, p = 0.02) significantly reduced the P300 amplitude. A similar trend was also found in BZP. In contrast, BZP and TFMPP in combination has no effect. Neither P300 latency nor the mean reaction time was affected by any of the drug treatments. In addition, neither the P100 nor the P200 component was significantly affected following any of the drug treatments.

Conclusions

A single oral dose of BZP or TFMPP, but not the combination of BZP/TFMPP, affected auditory sensory-evoked P300 potential in a manner similar to dexamphetamine.

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References

  • Alarcon G, Guy CN, Binnie CD (2000) A simple algorithm for a digital three-pole Butterworth filter of arbitrary cut-off frequency: application to digital electroencephalography. J Neurosci Methods 104(1):35–44

    Article  CAS  PubMed  Google Scholar 

  • Albrecht MA, Martin-Iverson MT, Price G, Lee J, Iyyalol R (2011) Dexamphetamine-induced reduction of P3a and P3b in healthy participants. J Psychopharmacol 25(12):1623–1631

    Article  CAS  PubMed  Google Scholar 

  • Anokhin AP, Vedeniapin AB, Sirevaag EJ, Bauer LO, O’Connor SJ, Kuperman S et al (2000) The P300 brain potential is reduced in smokers. Psychopharmacology 149(4):409–413

    Article  CAS  PubMed  Google Scholar 

  • Antia U, Russell BR, Tingle MD (2009) Metabolic interactions with piperazine-based ‘party pill’ drugs. J Pharm Pharmacol 61:877–882

    CAS  PubMed  Google Scholar 

  • Auerbach SB, Kamalakannan N, Rutter JJ (1990) TFMPP and RU24969 enhance serotonin release from rat hippocampus. Eur J Pharmacol 190(1–2):51–57

    Article  CAS  PubMed  Google Scholar 

  • Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (2004) Effects of “Legal X” piperazine analogs on dopamine and serotonin release in rat brain. Ann N Y Acad Sci 1025:189–197

    Article  CAS  PubMed  Google Scholar 

  • Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB (2005) N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’). Neuropsychopharmacology 30(3):550–560

    Article  CAS  PubMed  Google Scholar 

  • Bye C, Munro-Faure AD, Peck AW, Young PA (1973) A comparison of the effects of 1-benzylpiperazine and dexamphetamine on human performance tests. Eur J Clin Pharmacol 6(3):163–169

    Article  CAS  PubMed  Google Scholar 

  • Callaway E (1984) Human information-processing: some effects of methylphenidate, age, and scopolamine. Biol Psychiatry 19(5):649–662

    CAS  PubMed  Google Scholar 

  • Campbell H, Cline W, Evans M, Lloyd J, Peck AW (1973) Comparison of the effects of dexamphetamine and 1-benzylpiperazine in former addicts. Eur J Clin Pharmacol 6(3):170–176

    Article  CAS  PubMed  Google Scholar 

  • Curley L, Kydd R, Robertson M, Pillai A, McNair N, Lee H et al. (2015) Acute effects of the designer drugs benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) using functional magnetic resonance imaging (fMRI) and the Stroop task—a pilot study. Psychopharmacology, 1–12

  • de Boer D, Bosman IJ, Hidvegi E, Manzoni C, Benko AA, dos Reys LJ et al (2001) Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market. Forensic Sci Int 121(1–2):47–56

    Article  PubMed  Google Scholar 

  • Donchin E, Coles MGH (1988) Is the P300 component a manifestation of context updating? Behav Brain Sci 11:357–374

    Article  Google Scholar 

  • Fabiani M, Karis D, Donchin E (1990) Effects of mnemonic strategy manipulation in a Von Restorff paradigm. Electroencephalogr Clin Neurophysiol 75(2):22–35

    Article  CAS  PubMed  Google Scholar 

  • Fantegrossi WE, Kiessel CL, Leach PT, Van Martin C, Karabenick RL, Chen X et al (2004) Nantenine: an antagonist of the behavioral and physiological effects of MDMA in mice. Psychopharmacology (Berl) 173(3–4):270–277

    Article  CAS  Google Scholar 

  • 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(3):529–536

    Article  CAS  Google Scholar 

  • Geisler MW, Polich J (1990) P300 and time of day: circadian rhythms, food intake, and body temperature. Biol Psychol 31(2):117–136

    Article  CAS  PubMed  Google Scholar 

  • Gevins A, Smith ME, McEvoy LK (2002) Tracking the cognitive pharmacodynamics of psychoactive substances with combinations of behavioral and neurophysiological measures. Neuropsychopharmacology 26(1):27–39

    Article  CAS  PubMed  Google Scholar 

  • Halliday R, Naylor H, Brandeis D, Callaway E, Yano L, Herzig K (1994) The effect of D-amphetamine, clonidine, and yohimbine on human information processing. Psychophysiology 31(4):331–337

    Article  CAS  PubMed  Google Scholar 

  • Hansenne M, Pitchot W, Gonzalez Moreno A, Papart P, Timsit-Berthier M, Ansseau M (1995) Catecholaminergic function and P300 amplitude in major depressive disorder (P300 and catecholamines). Electroencephalogr Clin Neurophysiol 96(2):194–196

    Article  CAS  PubMed  Google Scholar 

  • Hausmann M, Hamm JP, Waldie KE, Kirk IJ (2013) Sex hormonal modulation of interhemispheric transfer time. Neuropsychologia 51(9):1734–1741

    Article  CAS  PubMed  Google Scholar 

  • Hill SY, Steinhauer S, Lowers L, Locke J (1995) Eight-year longitudinal follow-up of P300 and clinical outcome in children from high-risk for alcoholism families. Biol Psychiatry 37(11):823–827

    Article  CAS  PubMed  Google Scholar 

  • Hoyer D, Schoeffter P (1988) 5-HT1D receptor-mediated inhibition of forskolin-stimulated adenylate cyclase activity in calf substantia nigra. Eur J Pharmacol 147(1):145–147

    Article  CAS  PubMed  Google Scholar 

  • Jan RK, Lin JC, Lee H, Sheridan JL, Kydd RR, Kirk IJ et al (2010) Determining the subjective effects of TFMPP in human males. Psychopharmacology (Berl) 211(3):347–353

    Article  CAS  Google Scholar 

  • Jeon YW, Polich J (2003) Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications. Psychophysiology 40(5):684–701

    Article  PubMed  Google Scholar 

  • Jervis BW, Nichols MJ, Allen EM, Hudson NR, Johnson TE (1985) The assessment of two methods for removing eye movement artefact from the EEG. Electroencephalogr Clin Neurophysiol 61(5):444–452

    Article  CAS  PubMed  Google Scholar 

  • Johnson SW, Mercuri NB, North RA (1992) 5-hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons. J Neurosci 12(5):2000–2006

    CAS  PubMed  Google Scholar 

  • Kenemans JL, Kahkonen S (2011) How human electrophysiology informs psychopharmacology: from bottom-up driven processing to top-down control. Neuropsychopharmacology 36(1):26–51

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lazarev VV (2006) The relationship of theory and methodology in EEG studies of mental activity. Int J Psychophysiol 62(3):384–393

    Article  PubMed  Google Scholar 

  • Lee H, Kydd RR, Lim VK, Kirk IJ, Russell BR (2011) Effects of trifluoromethylphenylpiperazine (TFMPP) on interhemispheric communication. Psychopharmacology (Berl) 213(4):707–714

    Article  CAS  Google Scholar 

  • Lehmann D, Skrandies W (1980) Reference-free identification of components of checkerboard-evoked multichannel potential fields. Electroencephalogr Clin Neurophysiol 48(6):609–621

    Article  CAS  PubMed  Google Scholar 

  • Lin JC, Bangs N, Lee H, Kydd RR, Russell BR (2009) Determining the subjective and physiological effects of BZP on human females. Psychopharmacology (Berl) 207(3):439–446

    Article  CAS  Google Scholar 

  • Lin JC, Jan RK, Kydd RR, Russell BR (2011) Subjective effects in humans following administration of party pill drugs BZP and TFMPP alone and in combination. Drug Test Anal 3(9):582–585

    Article  CAS  PubMed  Google Scholar 

  • Magyar K, Fekete MI, Tekes K, Torok TL (1986) The action of trelibet, a new antidepressive agent on [3H]noradrenaline release from rabbit pulmonary artery. Eur J Pharmacol 130(3):219–227

    Article  CAS  PubMed  Google Scholar 

  • McKenney JD, Glennon RA (1986) TFMPP may produce its stimulus effects via a 5-HT1B mechanism. Pharmacol Biochem Behav 24(1):43–47

    Article  CAS  PubMed  Google Scholar 

  • Meririnne E, Kajos M, Kankaanpaa A, Seppala T (2006) Rewarding properties of 1-benzylpiperazine, a new drug of abuse, in rats. Basic Clin Pharmacol Toxicol 98(4):346–350

    Article  CAS  PubMed  Google Scholar 

  • Miele M, Mura MA, Enrico P, Esposito G, Serra PA, Migheli R et al (2000) On the mechanism of d-amphetamine-induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats. Br J Pharmacol 129(3):582–588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Muller TJ, Kalus P, Strik WK (2001) The neurophysiological meaning of auditory P300 in subtypes of schizophrenia. World J Biol Psychiatry 2(1):9–17

    Article  CAS  PubMed  Google Scholar 

  • Murray MM, Brunet D, Michel CM (2008) Topographic ERP analyses: a step-by-step tutorial review. Brain Topogr 20(4):249–264

    Article  PubMed  Google Scholar 

  • Nishimura N, Ogura C, Ohta I (1995) Effects of the dopamine-related drug bromocriptine on event-related potentials and its relation to the law of initial value. Psychiatry Clin Neurosci 49(1):79–86

    Article  CAS  PubMed  Google Scholar 

  • Nissbrandt H, Waters N, Hjorth S (1992) The influence of serotoninergic drugs on dopaminergic neurotransmission in rat substantia nigra, striatum and limbic forebrain in vivo. Naunyn Schmiedebergs Arch Pharmacol 346(1):12–19

    Article  CAS  PubMed  Google Scholar 

  • Nowicka A, Fersten E (2001) Sex-related differences in interhemispheric transmission time in the human brain. Neuroreport 12(18):4171–4175

    Article  CAS  PubMed  Google Scholar 

  • Oranje B, Gispen-de Wied CC, Westenberg HG, Kemner C, Verbaten MN, Kahn RS (2006) No effects of l-dopa and bromocriptine on psychophysiological parameters of human selective attention. J Psychopharmacol 20(6):789–798

    Article  CAS  PubMed  Google Scholar 

  • Polich J (2007) Updating P300: an integrative theory of P3a and P3b. Clin Neurophysiol 118(10):2128–2148

    Article  PubMed Central  PubMed  Google Scholar 

  • Polich J, Herbst KL (2000) P300 as a clinical assay: rationale, evaluation, and findings. Int J Psychophysiol 38(1):3–19

    Article  CAS  PubMed  Google Scholar 

  • Polich J, Kok A (1995) Cognitive and biological determinants of P300: an integrative review. Biol Psychol 41(2):103–146

    Article  CAS  PubMed  Google Scholar 

  • Pritchard W, Sokhadze E, Houlihan M (2004) Effects of nicotine and smoking on event-related potentials: a review. Nicotine Tob Res 6(6):961–984

    Article  CAS  PubMed  Google Scholar 

  • Skrandies W (2007) The effect of stimulation frequency and retinal stimulus location on visual evoked potential topography. Brain Topogr 20(1):15–20

    Article  PubMed  Google Scholar 

  • Srkalovic G, Selim M, Rea MA, Glass JD (1994) Serotonergic inhibition of extracellular glutamate in the suprachiasmatic nuclear region assessed using in vivo brain microdialysis. Brain Res 656(2):302–308

    Article  CAS  PubMed  Google Scholar 

  • Szucks Z, Szentendrei T, Fekete MI (1987) The effect of EGYT-475 (Trelibet) and its metabolites on the potassium-stimulated 3H-noradrenaline release from cortical slices of rat brain. Pol J Pharmacol Pharm 39(2):185–193

    CAS  PubMed  Google Scholar 

  • Verleger R (1988) Event-related potentials and cognition: a critique of the context updating hypothesis and an alternative interpretation of P3. Behav Brain Sci 11:343–427

    Article  Google Scholar 

  • Verleger R, Metzner MF, Ouyang G, Śmigasiewicz K, Zhou C (2014) Testing the stimulus-to-response bridging function of the oddball-P3 by delayed response signals and residue iteration decomposition (RIDE). NeuroImage 100:271–280

    Article  PubMed  Google Scholar 

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Acknowledgments

Special thanks to Michelle Robertson, Melissa Innes-Jones, Kristen Penny, Stephanie Taylor, James Millar and Lisa Wallace for their help with the data collection.

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Authors and Affiliations

  1. School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand

    HeeSeung Lee, Louise E. Curley & Bruce R. Russell

  2. Department of Psychology, Auckland University of Technology, Auckland, New Zealand

    Grace Y. Wang

  3. Department of Psychological Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    John J. Sollers & Rob R. Kydd

  4. Cognitive Neuroscience Research Group, School of Psychology, The University of Auckland, Auckland, New Zealand

    Rob R. Kydd & Ian J. Kirk

  5. Centre for Brain Research, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    HeeSeung Lee, Louise E. Curley, Ian J. Kirk & Bruce R. Russell

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  1. HeeSeung Lee
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Correspondence to Bruce R. Russell.

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Conflict of interest

The authors declare no conflict of interest in this research. The Health Research Council of New Zealand and the New Zealand Pharmacy Education Research Foundation funded this research but had no influence on any part of research process or preparation of this manuscript.

Ethics approval and consent to participate

Following the provision of both written and oral information, written consent was obtained from all participants before enrolment in the study. This study received ethics approval from the Northern X Regional Ethics Committee of New Zealand.

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Lee, H., Wang, G.Y., Curley, L.E. et al. Acute effects of BZP, TFMPP and the combination of BZP and TFMPP in comparison to dexamphetamine on an auditory oddball task using electroencephalography: a single-dose study. Psychopharmacology 233, 863–871 (2016). https://doi.org/10.1007/s00213-015-4165-x

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  • DOI: https://doi.org/10.1007/s00213-015-4165-x

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