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Published on: February 5, 2018
Synthesis and pharmacological evaluation of ring-methylated derivatives of 3,4-(methylenedioxy)amphetamine (MDA)
M A Parker1, D Marona-Lewicka, D Kurrasch
1Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Abstract:
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.
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