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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.
Eur J Pharmacol 2006; 546(1-3):74-81EJ

Abstract

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 [(3)H]-paroxetine binding (SERT density) one week after final drug administration. When rats were housed at a higher ambient temperature (28 degrees C vs. 22 degrees 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.

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    Authors+Show Affiliations

    Callaghan PD
    Discipline of Pharmacology, School of Medical Sciences, Medical School North, The University of Adelaide, Adelaide, South Australia, 5005, Australia.
    Farrand K
    No affiliation info available
    Salem A
    No affiliation info available
    Hughes P
    No affiliation info available
    Daws LC
    No affiliation info available
    Irvine RJ
    No affiliation info available

    MeSH

    3,4-Dihydroxyphenylacetic AcidAmphetaminesAnimalsBinding, CompetitiveBrain ChemistryCerebral CortexChromatography, High Pressure LiquidDopamineDose-Response Relationship, DrugElectrochemistryHallucinogensHydroxyindoleacetic AcidMaleN-Methyl-3,4-methylenedioxyamphetamineParoxetineRatsRats, Sprague-DawleySerotoninSerotonin Plasma Membrane Transport ProteinsSerotonin Uptake InhibitorsSynaptic TransmissionTime Factors

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    16925993

    Citation

    Callaghan, Paul D., et al. "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." European Journal of Pharmacology, vol. 546, no. 1-3, 2006, pp. 74-81.
    Callaghan PD, Farrand K, Salem A, et al. 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. Eur J Pharmacol. 2006;546(1-3):74-81.
    Callaghan, P. D., Farrand, K., Salem, A., Hughes, P., Daws, L. C., & Irvine, R. J. (2006). 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. European Journal of Pharmacology, 546(1-3), pp. 74-81.
    Callaghan PD, et al. 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. Eur J Pharmacol. 2006 Sep 28;546(1-3):74-81. PubMed PMID: 16925993.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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. AU - Callaghan,Paul D, AU - Farrand,Kirsten, AU - Salem,Abdallah, AU - Hughes,Patrick, AU - Daws,Lynette C, AU - Irvine,Rodney J, Y1 - 2006/07/25/ PY - 2006/05/30/received PY - 2006/07/13/revised PY - 2006/07/17/accepted PY - 2006/8/24/pubmed PY - 2007/1/12/medline PY - 2006/8/24/entrez SP - 74 EP - 81 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 546 IS - 1-3 N2 - 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 [(3)H]-paroxetine binding (SERT density) one week after final drug administration. When rats were housed at a higher ambient temperature (28 degrees C vs. 22 degrees 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16925993/Repeated_administration_of_the_substituted_amphetamine_p_methoxyamphetamine_produces_reductions_in_cortical_5_HT_transporter_binding_but_not_5_HT_content_unlike_34_methylenedioxyamethamphetamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)00773-4 DB - PRIME DP - Unbound Medicine ER -
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