Tags

Type your tag names separated by a space and hit enter

Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters.
J Pharmacol Exp Ther. 2005 Jul; 314(1):346-54.JP

Abstract

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 microM. 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 microM, 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.

Authors+Show Affiliations

Center for Brain Research, Medical University of Vienna, Spitalgasse 4, A-1090 Vienna, Austria. christian.pifl@meduniwien.ac.atNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15831439

Citation

Pifl, Christian, et al. "Pharmacological Characterization of Ecstasy Synthesis Byproducts With Recombinant Human Monoamine Transporters." The Journal of Pharmacology and Experimental Therapeutics, vol. 314, no. 1, 2005, pp. 346-54.
Pifl C, Nagy G, Berényi S, et al. Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. J Pharmacol Exp Ther. 2005;314(1):346-54.
Pifl, C., Nagy, G., Berényi, S., Kattinger, A., Reither, H., & Antus, S. (2005). Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. The Journal of Pharmacology and Experimental Therapeutics, 314(1), 346-54.
Pifl C, et al. Pharmacological Characterization of Ecstasy Synthesis Byproducts With Recombinant Human Monoamine Transporters. J Pharmacol Exp Ther. 2005;314(1):346-54. PubMed PMID: 15831439.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological characterization of ecstasy synthesis byproducts with recombinant human monoamine transporters. AU - Pifl,Christian, AU - Nagy,Gabor, AU - Berényi,Sándor, AU - Kattinger,Alexandra, AU - Reither,Harald, AU - Antus,Sándor, Y1 - 2005/04/14/ PY - 2005/4/16/pubmed PY - 2005/8/27/medline PY - 2005/4/16/entrez SP - 346 EP - 54 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 314 IS - 1 N2 - 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 microM. 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 microM, 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15831439/Pharmacological_characterization_of_ecstasy_synthesis_byproducts_with_recombinant_human_monoamine_transporters_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15831439 DB - PRIME DP - Unbound Medicine ER -