Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters

Christian Pifl, Gabor Nagy, Sándor Berényi, Alexandra Kattinger, Harald Reither, S. Antus

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Ecstasy samples often contain byproducts of the illegal, uncontrolled synthesis of N-methyl-3,4-methylenedioxy-amphetamine or 3,4-methylenedioxy- methamphetamine (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)]. SKN-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.

Original languageEnglish
Pages (from-to)346-354
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume314
Issue number1
DOIs
Publication statusPublished - Jul 2005

Fingerprint

Methamphetamine
Pharmacology
Norepinephrine Plasma Membrane Transport Proteins
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
Inhibitory Concentration 50
Nitro Compounds
1-Methyl-4-phenylpyridinium
Amphetamine
Structure-Activity Relationship
Neuroblastoma
Amines
Complementary DNA
Kidney

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. / Pifl, Christian; Nagy, Gabor; Berényi, Sándor; Kattinger, Alexandra; Reither, Harald; Antus, S.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 314, No. 1, 07.2005, p. 346-354.

Research output: Contribution to journalArticle

Pifl, Christian ; Nagy, Gabor ; Berényi, Sándor ; Kattinger, Alexandra ; Reither, Harald ; Antus, S. / Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. In: Journal of Pharmacology and Experimental Therapeutics. 2005 ; Vol. 314, No. 1. pp. 346-354.
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