Synthesis and Pharmacological Evaluation of Ring-Methylated Derivatives of 3,4-(Methylenedioxy)amphetamine (MDA)
Matthew Parker, Danuta Marona‐lewicka, Deborah M. Kurrasch, Alexander T. Shulgin, David E. Nichols
Journal of Medicinal Chemistry February 24, 1998 DOI: 10.1021/jm9705925 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo and in vitro pharmacological study Peer reviewed |
|---|---|
| Population | Rat brain synaptosomal preparations and live rats |
| Topics | Serotonin |
| Keywords | Methylenedioxy Pharmacology Hallucinogen Amphetamine In vivo Stereochemistry Antidepressant Monoamine neurotransmitter Amitriptyline Biochemistry Receptor Dopamine Hippocampus Organic chemistry |
| Citations | 25 |
| Key points | The 2-methyl and 5-methyl derivatives of MDA are more potent and selective than MDA in releasing serotonin and are among the most potent serotonin-releasing compounds known. |
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.