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Synthetic cathinones are the second largest NPS group, often mimicking the effects of classical stimulants such as cocaine and methylenedioxymethamphetamine (MDMA). Such stimulants primarily target dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters, with DAT selectivity being linked to abuse potential. Owing to the lack of pharmacological profiling, this study aimed to determine the potencies and structure\u2013activity relationships (SARs) of recently emerged stimulants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Employing in vitro human transporter inhibition assay and AequoScreen\u00ae 5\u2010HT\n                      <jats:sub>2A<\/jats:sub>\n                      receptor activity assay, the potency, transporter selectivity, DAT\/SERT, DAT\/NET, and NET\/SERT ratios, and group\u2010wide SARs of 58 substances were investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Most synthetic cathinones inhibited DAT at nanomolar concentrations, with N\u2010pyrrolidine cathinones in combination with methylenedioxy groups\u20144\u2010methylenedioxy\u2010\u03b1\u2010pyrrolidino\u2010isohexanophenone (MDPiHP), 3,4\u2010methylenedioxy PV8 (MDPEP), and 3,4\u2010methylenedioxy pyrovalerone (MDPV)\u2014demonstrating the highest DAT potency among all the tested stimulants. In contrast, other\n                      <jats:italic>N<\/jats:italic>\n                      \u2010pyrrolidine cathinones, 3F\u2010\u03b1\u2010PHP, 3F\u2010\u03b1\u2010PiHP and 4F\u2010\u03b1\u2010PiHP, exhibited the highest DAT selectivity (DAT\/SERT ratio). Chloromethcathinone (CMC) and methylmethcathinone (MMC) compounds, such as 3\u2010CMC, exhibited a distinct amphetamine\u2010like pharmacological uptake inhibition profile showing a comparable potency between DAT and NET. Some cathinones at high concentrations and phenethylamines in micromolar concentrations additionally activated the 5\u2010HT\n                      <jats:sub>2A<\/jats:sub>\n                      receptor, whereas 2C\u2010like arylcyclohexylamines primarily targeted the receptor without transporter inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These results show that cathinones displayed distinct group SARs. Based on the DAT\/SERT selectivity, the majority of the investigated compounds, especially N\u2010pyrrolidine cathinones, suggest a high abuse potential.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70587","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:03:40Z","timestamp":1784084620000},"page":"5871-5894","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive in vitro profiling of traditional and emerging stimulants at monoamine transporters and the 5\u2010HT\n                    <sub>2A<\/sub>\n                    receptor"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6712-652X","authenticated-orcid":false,"given":"Darta","family":"Stalberga","sequence":"first","affiliation":[{"name":"Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences Link\u00f6ping University  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