QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.084426v1 314/1/346    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pifl, C. Articles by Antus, S. Search for Related Content PubMed PubMed Citation Articles by Pifl, C. Articles by Antus, S.

NEUROPHARMACOLOGY

Pharmacological Characterization of Ecstasy Synthesis Byproducts with Recombinant Human Monoamine Transporters

Center for Brain Research, Medical University of Vienna, Austria (C.P., A.K., H.R.); Institute of Pharmacognosy, University of Szeged, Hungary (G.N.); and Institute of Organic Chemistry, University of Debrecen, Hungary (S.B., S.A.)

Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxymethamphetamine (MDMA). MDMA and eight chemically defined byproducts of MDMA synthesis were investigated for their interaction with the primary sites of action of MDMA, namely the human plasmalemmal monamine transporters for norepinephrine, serotonin, and dopamine [(norepinephrine transporter (NET), serotonin transporter (SERT), and dopamine transporter (DAT)]. SK-N-MC neuroblastoma and human embryonic kidney cells stably transfected with the transporter cDNA were used for uptake and release experiments. Two of the eight compounds, 1,3-bis (3,4-methylenedioxyphenyl)-2-propanamine (12) and N-formyl-1,3-bis (3,4-methylenedioxyphenyl)-prop-2-yl-amine (13) had uptake inhibitory potencies with IC₅₀ values in the low micromolar range similar to MDMA. Compounds with nitro instead of amino groups and a phenylethenyl instead of a phenylethyl structure or a formamide or acetamide modification had IC₅₀ values beyond 100 µM. MDMA, 12, and 13 were examined for induction of carrier-mediated release by superfusion of transporter expressing cells preloaded with the metabolically inert transporter substrate [³H]1-methyl-4-phenylpyridinium. MDMA induced release mediated by NET, SERT, or DAT with EC₅₀ values of 0.64, 1.12, and 3.24 µM, respectively. 12 weakly released from NET- and SERT-expressing cells with maximum effects less than one-tenth of that of MDMA and did not release from DAT cells. 13 had no releasing activity. 12 and 13 inhibited release induced by MDMA, and the concentration dependence of this effect correlated with their uptake inhibitory potency at the various transporters. These results do not support a neurotoxic potential of the examined ecstasy synthesis byproducts and provide interesting structure-activity relationships on the transporters.

Address correspondence to: Dr. Christian Pifl, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. E-mail: christian.pifl{at}meduniwien.ac.at