Pharmacological characterization of 3,4-methylenedioxyamphetamine (MDA) analogs and two amphetamine-based compounds: ,α-DEPEA and DPIA
Karolina E. Kolaczynska, Paula Ducret, Daniel Trachsel, Marius C. Hoener, Matthias E. Liechti, Dino Luethi
European Neuropsychopharmacology April 1, 2022 DOI: 10.1016/j.euroneuro.2022.03.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study Peer reviewed |
|---|---|
| Population | Human embryonic kidney 293 cells stably transfected with human monoamine transporters |
| Interventions | MDA fluorinated MDA analogs BDB DPIA 3C-BOH N α-DEPEA |
| Topics | MDMA Serotonin |
| Keywords | Pharmacology Monoamine neurotransmitter Amphetamine Receptor Dopaminergic Dopamine transporter Stimulant |
| Citations | 7 |
| Key points | MDA analogs and related compounds show distinct pharmacological profiles: most inhibit norepinephrine uptake most potently and preferentially block serotonin over dopamine uptake, while 3C-BOH and N,α-DEPEA favor dopamine uptake and resemble amphetamine. |
Abstract
3,4-methylenedioxyamphetamine (MDA) is a psychoactive compound chemically related to the entactogen MDMA. MDA shares some of the entactogenic effects of MDMA but also exerts stimulant effects and psychedelic properties at higher doses. Here, we examined the pharmacological properties of MDA analogs and related amphetamine-based compounds detected in street drug samples or in sport supplements. We examined the key pharmacological mechanisms including monoamine uptake inhibition and release using human embryonic kidney 293 cells stably transfected with the respective human transporters. Additionally, we assessed monoamine transporter and receptor binding and activation properties. MDA, its fluorinated analogs, as well as the α-ethyl containing BDB and the dimeric amphetamine DPIA inhibited NET with the greatest potency and preferentially inhibited 5-HT vs. dopamine uptake. The β‑methoxy MDA analog 3C-BOH and the amphetamine-based N,α-DEPEA inhibited NET and preferentially inhibited dopamine vs. 5-HT uptake. The test drugs mediated efflux of at least one monoamine with the exception of DPIA. Most compounds bound to 5-HT2A and 5-HT2C receptors (Ki ≤ 10 µM) and several substances activated the 5-HT2A and 5-HT2B receptor as partial or full agonists. Furthermore, several compounds interacted with adrenergic receptors and the trace amine-associated receptor 1 (TAAR1) in the micromolar range. The pharmacological profiles of some fluorinated and nonfluorinated MDA analogs resemble the profile of MDMA. In contrast, 3C-BOH and N,α-DEPEA displayed more pronounced dopaminergic activity similar to amphetamine. Pharmacokinetics and pharmacodynamics studies are necessary to better establish the risks and therapeutic potential of the tested drugs.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 5
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics. Neurochemical Research April 1, 2023
- Bioisosteric analogs of MDMA: Improving the pharmacological profile? Journal of Neurochemistry September 1, 2024
- Pathway-selective signaling of serotonergic psychedelics at 5-HT receptors: Implications for psychoactivity, safety, and therapeutic potential European Neuropsychopharmacology April 10, 2026
- Bioisosteric analogs of MDMA with improved pharmacological profile. bioRxiv : the preprint server for biology April 11, 2024
- Uncovering Structure-Activity Relationships of Phenethylamines: Paving the Way for Innovative Mental Health Treatments. ACS Chemical Neuroscience February 21, 2024
Cites 33
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and 28 more in the library