Journal article Open Access

Effects of "Legal X" Piperazine Analogs on Dopamine and Serotonin Release in Rat Brain

Baumann, Michael H.; Clark, Robert D.; Budzynski, Allison G.; Partilla, John S.; Blough, Bruce E.; Rothman, Richard B.


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{
  "DOI": "10.1196/annals.1316.024", 
  "author": [
    {
      "family": "Baumann, Michael H."
    }, 
    {
      "family": "Clark, Robert D."
    }, 
    {
      "family": "Budzynski, Allison G."
    }, 
    {
      "family": "Partilla, John S."
    }, 
    {
      "family": "Blough, Bruce E."
    }, 
    {
      "family": "Rothman, Richard B."
    }
  ], 
  "issued": {
    "date-parts": [
      [
        2004, 
        10, 
        1
      ]
    ]
  }, 
  "abstract": "3,4\u2010Methylenedioxymethamphetamine (MDMA) is a popular illicit drug that evokes transporter\u2010mediated release of serotonin (5\u2010HT) and dopamine (DA) from nerve cells. Recently, drug users have ingested combinations of the piperazine analogs, 1\u2010benzylpiperazine (BZP) and 1\u2010(m\u2010trifluoromethylphenyl)piperazine (TFMPP), in an attempt to mimic the subjective effects of MDMA. In the present study, we compared neurochemical effects of MDMA, BZP, and TFMPP in rat brain. The ability of MDMA, BZP, and TFMPP to stimulate efflux of [3H]5\u2010HT and [3H]MPP+ (a DA transporter substrate) was determined in vitro using release assays in synaptosomes. The ability of these drugs to increase extracellular 5\u2010HT and DA in vivo was assessed using intracranial microdialysis in nucleus accumbens. MDMA stimulated transporter\u2010mediated release of 5\u2010HT (EC50= 58 nM) and MPP+ (EC50= 119 nM). BZP was a selective releaser of MPP+ (EC50= 175 nM), whereas TFMPP was a selective releaser of 5\u2010HT (EC50= 121 nM). MDMA injections (1 and 3 mg/kg, i.v.) increased dialysate 5\u2010HT and DA in a dose\u2010related manner, but actions on 5\u2010HT were predominant. BZP (3 and 10 mg/kg, i.v.) elevated dialysate DA and 5\u2010HT, while TFMPP (3 and 10 mg/kg, i.v.) elevated only 5\u2010HT. The coadministration of BZP plus TFMPP (BZP/TFMPP) produced marked elevations in extracellular 5\u2010HT and DA that mirrored the effects of MDMA. At the high dose of BZP/TFMPP (10 mg/kg, i.v.), the rise in dialysate DA exceeded the summed effects of the drugs alone. Our results support the hypothesis that the BZP/TFMPP combination mimics the neurochemical mechanism of MDMA, providing a basis for recreational use of these agents. Additionally, the findings suggest possible drug\u2010drug synergism when piperazine drugs are coadministered at high doses.", 
  "title": "Effects of \"Legal X\" Piperazine Analogs on Dopamine and Serotonin Release in Rat Brain", 
  "type": "article-journal", 
  "id": "1235872"
}
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