Repeated administration of the substituted amphetamine p-methoxyamphetamine produces reductions in cortical 5-HT transporter binding but not 5-HT content, unlike 3,4-methylenedioxyamethamphetamine

Paul D. Callaghan, Kirsten Farrand, Abdallah Salem, Patrick Hughes, Lynette C. Daws, Rodney J. Irvine

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7 Citations (Scopus)


Worldwide growth in p-methoxyamphetamine (PMA) usage amongst 'ecstasy' users indicates a proportionally greater incidence of acute toxicity compared to 3,4-methylenedioxymethamphetamine (MDMA). While longer-term use of MDMA appears to produce degeneration of 5-hydroxytryptamine (5-HT, serotonin) neurons, PMA effects are poorly understood. The aim of this study was to determine the effect of repeated PMA administration on two indices of 5-HT axonal degeneration, cortical brain 5-HT transporter (SERT) density and 5-HT/5-hydroxyindolacetic acid (5-HIAA) content. Treatment of male rats once daily for 4 days (10 or 20 mg/kg) with PMA or MDMA resulted in significant reductions (20 mg/kg: 53% and 23% of vehicle treatment respectively) in [3H]-paroxetine binding (SERT density) one week after final drug administration. When rats were housed at a higher ambient temperature (28 °C vs. 22 °C) for 6 h after dosing, no additive effect was seen for either drug. A more intensive dosing regimen (10 or 20 mg/kg twice daily for 4 days) was used to examine PMA/MDMA effects on cortical 5-HT content. Two weeks after MDMA treatment, significant reductions in cortical 5-HT content (20 mg/kg: 39% of vehicle treatment) were seen. However, PMA did not alter cortical 5-HT content, yet reduced cortical 5-HIAA content (20 mg/kg: 72% of vehicle treatment). These data suggest PMA has severe long-term implications clinically for alteration of 5-HT neurotransmission that may differ from MDMA, but may not necessarily be interpreted as a degeneration of 5-HT fibres.

Original languageEnglish
Pages (from-to)74-81
Number of pages8
JournalEuropean Journal of Pharmacology
Issue number1-3
Publication statusPublished or Issued - 28 Sep 2006
Externally publishedYes


  • 3,4-methylenedioxymethamphetamine
  • 5-HT
  • Neurodegeneration
  • Para-methoxyamphetamine
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology

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