Synthesis and pharmacological evaluation of ring-methylated derivatives of 3,4-(methylenedioxy)amphetamine (MDA)

J Med Chem. 1998 Mar 12;41(6):1001-5. doi: 10.1021/jm9705925.


The three isomeric ring-methylated derivatives of the well-known hallucinogen and entactogen MDA (1a) were synthesized and evaluated for pharmacological activity as monoamine-releasing agents and as serotonin agonists. The 2-methyl derivative 2a and the 5-methyl derivative 2b were found to be more potent and more selective than the parent compound in inhibiting [3H]-serotonin accumulation in rat brain synaptosomal preparations. Their activity in vivo was confirmed in rats trained to discriminate serotonin-releasing agents and hallucinogens from saline. The results indicate that compounds 2a,b are among the most potent 5-HT-releasing compounds known and show promise as lead compounds in the search for antidepressant drugs that release serotonin rather than inhibit its uptake.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Methylenedioxyamphetamine / pharmacology*
  • Animals
  • Antidepressive Agents / chemical synthesis
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Brain / ultrastructure
  • Dioxoles / chemical synthesis
  • Dioxoles / pharmacology*
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Agents / chemical synthesis
  • Serotonin Agents / pharmacology*
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism


  • 1-(4-methyl-1,3-benzodioxol-5-yl)-2-aminopropane
  • 1-(4-methyl-1,3-benzodioxol-6-yl)-2-aminopropane
  • Antidepressive Agents
  • Dioxoles
  • Serotonin Agents
  • 3,4-Methylenedioxyamphetamine