2. Academic Validation
  3. 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

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. doi: 10.1016/j.bmc.2015.07.035.
Fabio Del Bello 1,  Farhana Sakloth 1,  John S Partilla 2,  Michael H Baumann 2,  Richard A Glennon 3
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298, USA.
  • 2 Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Box 980540, Richmond, VA 23298, USA. Electronic address: [email protected].
PMID: 26233799 DOI: 10.1016/j.bmc.2015.07.035
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.

Keywords

DAT; MDMA; MDMC; NET; SERT.

Figures
Products