Non-neurotoxic amphetamine derivatives release serotonin through serotonin transporters.
Molecular Pharmacology February 1, 1993 DOI: 10.1016/s0026-895x(25)13609-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Platelet plasma membrane vesicles and chromaffin granule membrane vesicles, plus cells expressing dopamine transporters |
| Interventions | 3-Methoxy-4-methylamphetamine (MMA) 5-methoxy-6-methyl-2-aminoindan (MMAI) |
| Measures | imipramine binding, Na+ gradient-driven serotonin transport, [3H]serotonin release, vesicular biogenic amine transporter activity, transmembrane pH difference (delta pH), cocaine analog binding to dopamine transporter, dopamine release |
| Topics | Serotonin |
| Keywords | Chromaffin granules Nerve endings Blood platelets Cell membrane Humans Amphetamines Methamphetamine Imipramine Indans Carrier proteins Membrane transport proteins Membrane glycoproteins Nerve tissue proteins Radioligand assay Models, biological In vitro techniques |
| Key points | MMA and MMAI, though reported as non-neurotoxic, released [3H]serotonin from plasma membrane vesicles by an exchange process at half-maximal concentrations comparable to those reported for MDMA, and both inhibited vesicular serotonin transport. At higher concentrations they also released serotonin from chromaffin granule vesicles and dissipated the transmembrane pH difference. Unlike MDMA and methamphetamine, MMAI did not inhibit dopamine transporter binding or dopamine release. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA) and several other amphetamine derivatives cause degeneration of serotonergic nerve terminals. These drugs also release serotonin from nerve terminals both in vivo and in vitro. Two non-neurotoxic derivatives of MDMA were tested in membrane vesicle model systems to determine whether they also lacked the ability to release serotonin. 3-Methoxy-4-methylamphetamine (MMA) and 5-methoxy-6-methyl-2-aminoindan (MMAI) both inhibited imipramine binding to serotonin transporters in platelet plasma membrane vesicles and both inhibited Na+ gradient-driven serotonin transport into those vesicles. Significantly, both MMA and MMAI released [3H]serotonin from plasma membrane vesicles, apparently by a process of exchange. The half-maximal concentrations for this effect were comparable to that reported for MDMA. In addition to their effects on plasma membrane transporters, MMA and MMAI both inhibited serotonin transport into chromaffin granule membrane vesicles catalyzed by the vesicular biogenic amine transporter. At higher concentrations, these compounds also caused release of [3H]serotonin from chromaffin granule membrane vesicles and dissipated the transmembrane pH difference (delta pH). Although MMAI effects on the serotonin transporter were similar to those of MDMA, the two compounds had different effects on dopamine transporters. MDMA and methamphetamine inhibited binding of a cocaine analog to the dopamine transporter and released dopamine accumulated by cells expressing dopamine transporters, but similar concentrations of MMAI were inactive.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 5
- The abused drug MDMA (Ecstasy) induces programmed death of human serotonergic cells The FASEB Journal February 1, 1997
- Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-aminoindan. European Journal of Pharmacology June 2, 1994
- Pharmacological profile of mephedrone analogs and related new psychoactive substances. Neuropharmacology May 15, 2018
- The external gate of the human and Drosophila serotonin transporters requires a basic/acidic amino acid pair for 3,4-methylenedioxymethamphetamine (MDMA) translocation and the induction of substrate efflux Biochemical Pharmacology September 13, 2016
- Mice in ecstasy: advanced animal models in the study of MDMA. Current Pharmaceutical Biotechnology August 1, 2010