ArticleBritish journal of pharmacology2014
A quantitative model of amphetamine action on the 5-HT transporter.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 37 citations in OpenAlex.
- Electrophysiological Methods to Explore the Function of Monoamine Transporters.Advances in neurobiology · 2025Review
- Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring.Journal of neurochemistry · 2024Article
- Identification of the potassium-binding site in serotonin transporter.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Applications and Potential of In Silico Approaches for Psychedelic Chemistry.Molecules (Basel, Switzerland) · 2023Review
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- 3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs.Frontiers in psychiatry · 2022Review
- Descriptors of Secondary Active Transporter Function and How They Relate to Partial Reactions in the Transport Cycle.Membranes · 2021Article
- Serotonin transport in the 21st century.The Journal of general physiology · 2019Review
- Kinetic Models of Secondary Active Transporters.International journal of molecular sciences · 2019Article
- The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice.International journal of molecular sciences · 2019Review
- The synthetic cathinones, butylone and pentylone, are stimulants that act as dopamine transporter blockers but 5-HT transporter substrates.Psychopharmacology · 2019Article
- An unsuspected role for organic cation transporter 3 in the actions of amphetamine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Article
- A kinetic account for amphetamine-induced monoamine release.The Journal of general physiology · 2018Article
- Conformational state interactions provide clues to the pharmacochaperone potential of serotonin transporter partial substrates.The Journal of biological chemistry · 2017Article
- Occupancy of the Zinc-binding Site by Transition Metals Decreases the Substrate Affinity of the Human Dopamine Transporter by an Allosteric Mechanism.The Journal of biological chemistry · 2017Article
- The N Terminus Specifies the Switch between Transport Modes of the Human Serotonin Transporter.The Journal of biological chemistry · 2017Article
- Electrophysiological Actions of Synthetic Cathinones on Monoamine Transporters.Current topics in behavioral neurosciences · 2017Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAmphetamines bind to the plasmalemmal transporters for the monoamines dopamine (DAT), noradrenaline (NET) and 5-HT (SERT); influx of amphetamine leads to efflux of substrates. Various models have been proposed to account for this amphetamine-induced reverse transport in mechanistic terms. A most notable example is the molecular stent hypothesis, which posits a special amphetamine-induced conformation that is not likely in alternative access models of transport. The current study was designed to evaluate the explanatory power of these models and the molecular stent hypothesis. EXPERIMENTAL APPROACH: Xenopus laevis oocytes and HEK293 cells expressing human (h) SERT were voltage-clamped and exposed to 5-HT, p-chloroamphetamine (pCA) or methylenedioxyamphetamine (MDMA). KEY
resultsIn contrast to the currents induced by 5-HT, pCA-triggered currents through SERT decayed slowly in Xenopus laevis oocytes once the agonist was removed (consistent with the molecular stent hypothesis). However, when SERT was expressed in HEK293 cells, currents induced by 3 or 100 μM pCA decayed 10 or 100 times faster, respectively, after pCA removal. CONCLUSIONS AND IMPLICATIONS: This discrepancy in decay rates is inconsistent with the molecular stent hypothesis. In contrast, a multistate version of the alternative access model accounts for all the observations and reproduces the kinetic parameters extracted from the electrophysiological recordings. A crucial feature that explains the action of amphetamines is their lipophilic nature, which allows for rapid diffusion through the membrane.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.