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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.

Authors+Show Affiliations

Discipline of Pharmacology, School of Medical Sciences, Medical School North, The University of Adelaide, Adelaide, South Australia, 5005, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -