Amphetamine derivatives interact with both plasma membrane and secretory vesicle biogenic amine transporters.
S Schuldiner, S Steiner-Mordoch, R Yelin, S C Wall, Gary Rudnick
Molecular Pharmacology December 1, 1993 DOI: 10.1016/s0026-895x(25)13357-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro experimental study Peer reviewed |
|---|---|
| Population | Platelet plasma membrane preparations and adrenal chromaffin granule membrane vesicles (from cattle) |
| Interventions | Fenfluramine 3 4-Methylenedioxymethamphetamine (MDMA) p-Chloroamphetamine (PCA) |
| Measures | [3H]serotonin transport, imipramine binding, [3H]reserpine binding, transmembrane pH difference (delta pH) |
| Topics | Serotonin |
| Keywords | Chromaffin granules Blood platelets Cell membrane Animals Cattle Humans P-chloroamphetamine N-methyl-3,4-methylenedioxyamphetamine Fenfluramine Reserpine Carrier proteins Membrane transport proteins Membrane glycoproteins Nerve tissue proteins In vitro techniques |
| Key findings | Fenfluramine appears to act as a substrate for the platelet plasma membrane serotonin transporter, inhibiting serotonin transport and imipramine binding and exchanging with internal serotonin in an NaCl-dependent, imipramine-blocked reaction, like MDMA and PCA. In chromaffin granule vesicles, MDMA and fenfluramine inhibit vesicular serotonin transport both by directly blocking the transporter and by dissipating the transmembrane pH difference, whereas PCA dissipates the pH gradient without directly blocking vesicular amine transport. |
Abstract
The interaction of fenfluramine, 3,4-methylenedioxymethamphetamine (MDMA), and p-chloroamphetamine (PCA) with the platelet plasma membrane serotonin transporter and the vesicular amine transporter were studied using both transport and binding measurements. Fenfluramine is apparently a substrate for the plasma membrane transporter, and consequently inhibits both serotonin transport and imipramine binding. Moreover, fenfluramine exchanges with internal [3H]serotonin in a plasma membrane transporter-mediated reaction that requires NaCl and is blocked by imipramine. These properties are similar to those of MDMA and PCA as previously described. In adrenal chromaffin granule membrane vesicles containing the vesicular amine transporter, fenfluramine inhibited serotonin transport and dissipated the transmembrane pH difference (delta pH) that drives amine uptake. The use of [3H]reserpine-binding measurements to determine drug interaction with the vesicular amine transporter allowed assessment of the relative ability of MDMA, PCA, and fenfluramine to bind to the substrate site of the vesicular transporter. These measurements permit a distinction between inhibition of vesicular serotonin transport by directly blocking vesicular amine transport and by dissipating delta pH. The results indicate that MDMA and fenfluramine inhibit by both mechanisms but PCA dissipates delta pH without blocking vesicular amine transport directly.
Comparable studies
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| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
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| 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 8
- Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs BMC Pharmacology March 3, 2006
- Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine ACS Chemical Neuroscience July 12, 2018
- Cardiac effects of MDMA on the metabolic profile determined with 1H‐magnetic resonance spectroscopy in the rat NMR in Biomedicine November 4, 2008
- Neuroadaptive Changes in 5-HT1A Autoreceptor Sensitivity Following High-Dose MDMA Treatment 2011
- Psychedelic Therapy: A Primer for Primary Care Clinicians-3,4-Methylenedioxy-methamphetamine (MDMA). American Journal of Therapeutics
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