ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
'Second-generation' mephedrone analogs, 4-MEC and 4-MePPP, differentially affect monoamine transporter function.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Isolation, Characterization, and Stability Assessment of Pure Enantiomers of Cathinone Derivatives via Semi-Preparative HPLC-UV Using a Phenomenex LuxMolecules (Basel, Switzerland) · 2026Article
- Prolintane analogs as hybrid monoamine transporter ligands: Structural determinants and species differences.The Journal of biological chemistry · 2025Article
- Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties.Molecular psychiatry · 2024Article
- Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones.Neuropharmacology · 2024Article
- Structural and functional perspectives on interactions between synthetic cathinones and monoamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Development and validation of an automated microfluidic perfusion platform for parallelized screening of compounds in vitro.Basic & clinical pharmacology & toxicology · 2023Article
- Effects of Serial Polydrug Use on the Rewarding and Aversive Effects of the Novel Synthetic Cathinone Eutylone.Brain sciences · 2023Article
- Structure-Activity Relationships for a Recently Controlled Synthetic Cathinone Dopamine Transporter Reuptake Inhibitor: α-Pyrrolidinohexiophenone (α-PHP).ACS chemical neuroscience · 2023Article
- Neurochemical and Cardiovascular Effects of 4-Chloro Ring-Substituted Synthetic Cathinones in Rats.The Journal of pharmacology and experimental therapeutics · 2023Article
- Structure-Activity Relationship ofACS chemical neuroscience · 2023Article
- 4-Isobutylmethcathinone-A Novel Synthetic Cathinone with High In Vitro Cytotoxicity and Strong Receptor Binding Preference of Enantiomers.Pharmaceuticals (Basel, Switzerland) · 2022Article
- 3,4-Methylenedioxy methamphetamine, synthetic cathinones and psychedelics: From recreational to novel psychotherapeutic drugs.Frontiers in psychiatry · 2022Review
- Molecular mechanisms of action of stimulant novel psychoactive substances that target the high-affinity transporter for dopamine.Neuronal signaling · 2021Review
- An updated review on synthetic cathinones.Archives of toxicology · 2021Review
- Worsening of the Toxic Effects of (±)International journal of molecular sciences · 2021Article
- The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative.International journal of molecular sciences · 2021Article
- Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation.ACS chemical neuroscience · 2021Article
- Psychoactive Drugs-From Chemical Structure to Oxidative Stress Related to Dopaminergic Neurotransmission. A Review.Antioxidants (Basel, Switzerland) · 2021Review
- Effects of Hydroxylated Mephedrone Metabolites on Monoamine Transporter ActivityFrontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The nonmedical use of synthetic cathinones is increasing on a global scale. 4-Methyl-N-methylcathinone (mephedrone) is a popular synthetic cathinone that is now illegal in the United States and other countries. Since the legislative ban on mephedrone, a number of 'second-generation' analogs have appeared in the street drug marketplace, including 4-methyl-N-ethylcathinone (4-MEC) and 4'-methyl-α-pyrrolidinopropiophenone (4-MePPP). Here we characterized the interactions of 4-MEC and 4-MePPP with transporters for 5-HT (SERT) and dopamine (DAT) using molecular, cellular, and whole-animal methods. In vitro transporter assays revealed that 4-MEC displays unusual 'hybrid' activity as a SERT substrate (ie, 5-HT releaser) and DAT blocker, whereas 4-MePPP is a blocker at both transporters but more potent at DAT. In vivo microdialysis experiments in rat brain demonstrated that 4-MEC (1-3 mg/kg, i.v.) produced large increases in extracellular 5-HT, small increases in dopamine, and minimal motor stimulation. In contrast, 4-MePPP (1-3 mg/kg, i.v.) produced selective increases in dopamine and robust motor stimulation. Consistent with its activity as a SERT substrate, 4-MEC evoked inward current in SERT-expressing Xenopus oocytes, whereas 4-MePPP was inactive in this regard. To examine drug-transporter interactions at the molecular level, we modeled the fit of 4-MEC and 4-MePPP into the binding pockets for DAT and SERT. Subtle distinctions in ligand-transporter binding were found that account for the differential effects of 4-MEC and 4-MePPP at SERT. Collectively, our results provide key information about the pharmacology of newly emerging mephedrone analogs, and give clues to structural requirements that govern drug selectivity at DAT vs SERT.
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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.