{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T18:21:41Z","timestamp":1788200501334,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["16.921318"],"award-info":[{"award-number":["16.921318"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pyrovalerone cathinones are potent psychoactive substances that possess a pyrrolidine moiety. Pyrovalerone-type novel psychoactive substances (NPS) are continuously detected but their pharmacology and toxicology are largely unknown. We assessed several pyrovalerone and related cathinone derivatives at the human norepinephrine (NET), dopamine (DAT), and serotonin (SERT) uptake transporters using HEK293 cells overexpressing each respective transporter. We examined the transporter-mediated monoamine efflux in preloaded cells. The receptor binding and activation potency was also assessed at the 5-HT1A, 5-HT2A, 5-HT2B, and 5-HT2C receptors. All pyrovalerone cathinones were potent DAT (IC50 = 0.02\u20138.7 \u03bcM) and NET inhibitors (IC50 = 0.03\u20134.6 \u03bcM), and exhibited no SERT activity at concentrations &lt; 10 \u03bcM. None of the compounds induced monoamine efflux. NEH was a potent DAT\/NET inhibitor (IC50 = 0.17\u20130.18 \u03bcM). 4F-PBP and NEH exhibited a high selectivity for the DAT (DAT\/SERT ratio = 264\u2013356). Extension of the alkyl chain enhanced NET and DAT inhibition potency, while presence of a 3,4-methylenedioxy moiety increased SERT inhibition potency. Most compounds did not exhibit any relevant activity at other monoamine receptors. In conclusion, 4F-PBP and NEH were selective DAT\/NET inhibitors indicating that these substances likely produce strong psychostimulant effects and have a high abuse liability.<\/jats:p>","DOI":"10.3390\/ijms22158277","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:51:07Z","timestamp":1627854667000},"page":"8277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["The Pharmacological Profile of Second Generation Pyrovalerone Cathinones and Related Cathinone Derivative"],"prefix":"10.3390","volume":"22","author":[{"given":"Karolina E.","family":"Kolaczynska","sequence":"first","affiliation":[{"name":"Division of Psychopharmacology Research, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Thomann","sequence":"additional","affiliation":[{"name":"Division of Psychopharmacology Research, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius C.","family":"Hoener","sequence":"additional","affiliation":[{"name":"Neuroscience Research, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1765-9659","authenticated-orcid":false,"given":"Matthias E.","family":"Liechti","sequence":"additional","affiliation":[{"name":"Division of Psychopharmacology Research, Department of Biomedicine, University Hospital Basel and University of Basel, 4031 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.forsciint.2013.04.015","article-title":"Designer cathinones-an emerging class of novel recreational drugs","volume":"231","author":"Zawilska","year":"2013","journal-title":"Forensic Sci. 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