Comparative potencies of 3,4‐methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5‐HT transport in mammalian cell lines
Therese Montgomery, Christophe Buon, S Eibauer, Patrick J. Guiry, A. K. Keenan, Gethin J. Mcbean
British Journal of Pharmacology September 24, 2007 DOI: 10.1038/sj.bjp.0707473 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Rat PC12 cells expressing the noradrenaline transporter and HEK293 cells stably transfected with the serotonin transporter |
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Methylenedioxy Norepinephrine transporter Designer drug Hallucinogen |
| Citations | 33 |
| Key findings | 2,3-MDMA was less potent than MDMA at the serotonin transporter but equally potent at the noradrenaline transporter, while 2CB and BDB were less potent at the noradrenaline transporter but equally potent at the serotonin transporter. |
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 [ 3 H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [ 3 H]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. British Journal of Pharmacology (2007) 152 , 1121–1130; doi: 10.1038/sj.bjp.0707473 ; published online 24 September 2007