Synthesis and pharmacological evaluation of ring-methylated derivatives of 3,4-(methylenedioxy)amphetamine (MDA).
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.
Parker
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MA
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Marona-Lewicka
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D
Kurrasch
D
D
Shulgin
A T
AT
Nichols
D E
DE
D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004149:Dioxoles / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018490:Serotonin Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
C111361:1-(4-methyl-1,3-benzodioxol-5-yl)-2-aminopropane; C111362:1-(4-methyl-1,3-benzodioxol-6-yl)-2-aminopropane; D000928:Antidepressive Agents; D004149:Dioxoles; D018490:Serotonin Agents; D015104:3,4-Methylenedioxyamphetamine