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.
Comparable studies
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| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cited by 7
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- MDMA (3,4-Methylenedioxymethamphetamine) Analogues as Tools to Characterize MDMA-Like Effects: An Approach to Understand Entactogen Pharmacology Current Neuropharmacology August 1, 2013
- Fluorine in psychedelic phenethylamines Drug Testing and Analysis February 28, 2012
- Behavioral profiles in rats distinguish among "ecstasy," methamphetamine and 2,5-dimethoxy-4-iodoamphetamine: Mixed effects for "ecstasy" analogues. Behavioral Neuroscience October 1, 2010
- Aromatic Bromination Abolishes the Psychomotor Features and Pro-social Responses of MDMA ("Ecstasy") in Rats and Preserves Affinity for the Serotonin Transporter (SERT). Frontiers in Pharmacology February 28, 2019
and 2 more in the library
Cites 10
- The Background and Chemistry of MDMA Journal of Psychoactive Drugs October 1, 1986
- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: representatives of a novel therapeutic class Journal of Medicinal Chemistry October 1, 1986
- Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain. Biochemical Pharmacology July 15, 1987
- Dihydrobenzofuran Analogues of Hallucinogens. 3. Models of 4-Substituted (2,5-Dimethoxyphenyl)alkylamine Derivatives with Rigidified Methoxy Groups Journal of Medicinal Chemistry 1996
- Nonneurotoxic tetralin and indan analogs of 3,4-(methylenedioxy)amphetamine (MDA) Journal of Medicinal Chemistry February 1, 1990
and 5 more in the library