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 – September 24, 2007
Source: OpenAlex
Summary
MDMA analogues exhibit varied potency in influencing neurotransmitter transporters, crucial for understanding their effects. In a study involving multiple compounds, 2,3-MDMA showed reduced potency at the serotonin transporter (SERT) compared to MDMA but matched its effectiveness at the norepinephrine transporter (NET). Notably, 2CB and BDB were less potent at NET but equivalent at SERT. Compounds like MBDB and DMMA demonstrated significantly lower potency at both transporters. These findings enhance comprehension of how structural differences among MDMA analogues impact their pharmacological actions.
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