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Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines.
Br J Pharmacol 2007; 152(7):1121-30BJ

Abstract

BACKGROUND AND PURPOSE

Illegal 'ecstasy' tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT).

EXPERIMENTAL APPROACH

Concentration-response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA).

KEY RESULTS

2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT.

CONCLUSIONS AND IMPLICATIONS

This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.

Authors+Show Affiliations

1School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.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

17891159

Citation

Montgomery, T, et al. "Comparative Potencies of 3,4-methylenedioxymethamphetamine (MDMA) Analogues as Inhibitors of [3H]noradrenaline and [3H]5-HT Transport in Mammalian Cell Lines." British Journal of Pharmacology, vol. 152, no. 7, 2007, pp. 1121-30.
Montgomery T, Buon C, Eibauer S, et al. Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. Br J Pharmacol. 2007;152(7):1121-30.
Montgomery, T., Buon, C., Eibauer, S., Guiry, P. J., Keenan, A. K., & McBean, G. J. (2007). Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. British Journal of Pharmacology, 152(7), pp. 1121-30.
Montgomery T, et al. Comparative Potencies of 3,4-methylenedioxymethamphetamine (MDMA) Analogues as Inhibitors of [3H]noradrenaline and [3H]5-HT Transport in Mammalian Cell Lines. Br J Pharmacol. 2007;152(7):1121-30. PubMed PMID: 17891159.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. AU - Montgomery,T, AU - Buon,C, AU - Eibauer,S, AU - Guiry,P J, AU - Keenan,A K, AU - McBean,G J, Y1 - 2007/09/24/ PY - 2007/9/25/pubmed PY - 2008/2/6/medline PY - 2007/9/25/entrez SP - 1121 EP - 30 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 152 IS - 7 N2 - BACKGROUND AND PURPOSE: Illegal 'ecstasy' tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT). EXPERIMENTAL APPROACH: Concentration-response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA). KEY RESULTS: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT. CONCLUSIONS AND IMPLICATIONS: This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/17891159/Comparative_potencies_of_34_methylenedioxymethamphetamine__MDMA__analogues_as_inhibitors_of_[3H]noradrenaline_and_[3H]5_HT_transport_in_mammalian_cell_lines_ L2 - https://doi.org/10.1038/sj.bjp.0707473 DB - PRIME DP - Unbound Medicine ER -