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Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine.
Bioorg Med Chem. 2015 Sep 01; 23(17):5574-9.BM

Abstract

N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; 'Ecstasy'; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(-) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET.

Authors+Show Affiliations

Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298, USA.Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298, USA.Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298, USA. Electronic address: glennon@vcu.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

26233799

Citation

Del Bello, Fabio, et al. "Ethylenedioxy Homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and Its Corresponding Cathinone Analog Methylenedioxymethcathinone: Interactions With Transporters for Serotonin, Dopamine, and Norepinephrine." Bioorganic & Medicinal Chemistry, vol. 23, no. 17, 2015, pp. 5574-9.
Del Bello F, Sakloth F, Partilla JS, et al. Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine. Bioorg Med Chem. 2015;23(17):5574-9.
Del Bello, F., Sakloth, F., Partilla, J. S., Baumann, M. H., & Glennon, R. A. (2015). Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine. Bioorganic & Medicinal Chemistry, 23(17), 5574-9. https://doi.org/10.1016/j.bmc.2015.07.035
Del Bello F, et al. Ethylenedioxy Homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and Its Corresponding Cathinone Analog Methylenedioxymethcathinone: Interactions With Transporters for Serotonin, Dopamine, and Norepinephrine. Bioorg Med Chem. 2015 Sep 1;23(17):5574-9. PubMed PMID: 26233799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethylenedioxy homologs of N-methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) and its corresponding cathinone analog methylenedioxymethcathinone: Interactions with transporters for serotonin, dopamine, and norepinephrine. AU - Del Bello,Fabio, AU - Sakloth,Farhana, AU - Partilla,John S, AU - Baumann,Michael H, AU - Glennon,Richard A, Y1 - 2015/07/23/ PY - 2015/05/14/received PY - 2015/07/07/revised PY - 2015/07/16/accepted PY - 2015/8/3/entrez PY - 2015/8/4/pubmed PY - 2016/6/21/medline KW - DAT KW - MDMA KW - MDMC KW - NET KW - SERT SP - 5574 EP - 9 JF - Bioorganic & medicinal chemistry JO - Bioorg. Med. Chem. VL - 23 IS - 17 N2 - N-Methyl-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA; 'Ecstasy'; 1) and its β-keto analog methylone (MDMC; 2) are popular drugs of abuse. Little is known about their ring-expanded ethylenedioxy homologs. Here, we prepared N-methyl-(3,4-ethylenedioxyphenyl)-2-aminopropane (EDMA; 3), both of its optical isomers, and β-keto EDMA (i.e., EDMC; 4) to examine their effects at transporters for serotonin (SERT), dopamine (DAT), and norepinephrine (NET). In general, ring-expansion of the methylenedioxy group led to a several-fold reduction in potency at all three transporters. With respect to EDMA (3), S(+)3 was 6-fold, 50-fold, and 8-fold more potent than its R(-) enantiomer at SERT, DAT, and NET, respectively. Overall, in the absence of a β-carbonyl group, the ethylenedioxy (i.e., 1,4-dioxane) substituent seems better accommodated at SERT than at DAT and NET. SN - 1464-3391 UR - https://www.unboundmedicine.com/medline/citation/26233799/Ethylenedioxy_homologs_of_N_methyl__34_methylenedioxyphenyl__2_aminopropane__MDMA__and_its_corresponding_cathinone_analog_methylenedioxymethcathinone:_Interactions_with_transporters_for_serotonin_dopamine_and_norepinephrine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0968-0896(15)00619-7 DB - PRIME DP - Unbound Medicine ER -