{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:02:21Z","timestamp":1760385741346,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T00:00:00Z","timestamp":1574208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006109","name":"Vedeck\u00e1 Grantov\u00e1 Agent\u00fara M\u0160VVa\u0160 SR a SAV","doi-asserted-by":"publisher","award":["VEGA 2\/0166\/16, VEGA 2\/0127\/18 and VEGA-2\/0046\/18"],"award-info":[{"award-number":["VEGA 2\/0166\/16, VEGA 2\/0127\/18 and VEGA-2\/0046\/18"]}],"id":[{"id":"10.13039\/501100006109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005357","name":"Agent\u00fara na Podporu V\u00fdskumu a V\u00fdvoja","doi-asserted-by":"publisher","award":["APVV-15-0037 and APVV-15-0388"],"award-info":[{"award-number":["APVV-15-0037 and APVV-15-0388"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010783","name":"Slovak Academy of Sciences","doi-asserted-by":"publisher","award":["2013 Scholarship Award to E. Dremencov"],"award-info":[{"award-number":["2013 Scholarship Award to E. Dremencov"]}],"id":[{"id":"10.13039\/100010783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>SMe1EC2M3 is a pyridoindole derivative related to the neuroleptic drug carbidine. Based on the structural similarities of SMe1EC2M3 and known serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitors, we hypothesized that this compound may also have triple reuptake inhibition efficacy and an antidepressant-like effect. PreADMET and Dragon software was used for in silico prediction of pharmacokinetics and pharmacodynamics of SMe1EC2M3. Forced swim test was used to evaluate its antidepressant-like effects. Extracellular in vivo electrophysiology was used to assess 5-HT, norepinephrine, and dopamine reuptake inhibition efficacy of SMe1EC2M3. PreADMET predicted reasonable intestinal absorption, plasma protein binding, and blood-brain permeability for SMe1EC2M3. Dragon forecasted its efficiency as an antidepressant. Using behavioral measurements, it was found that SMe1EC2M3 decreased immobility time and increase swimming time during the forced swim test (FST). Electrophysiological investigations showed that SMe1EC2M3 dose-dependently suppressed the excitability of 5-HT neurons of the dorsal raphe nucleus (DRN), norepinephrine neurons of the locus coeruleus (LC), and dopamine neurons of the ventral tegmental area (VTA). The SMe1EC2M3-induced suppression of 5-HT, norepinephrine, and dopamine neurons was reversed by the antagonists of serotonin-1A (5-HT1A; WAY100135), \u03b1-2 adrenergic (\u03b12, yohimbine), and dopamine-2 receptors (D2, haloperidol), respectively. We conclude that SMe1EC2M3 is prospective triple 5-HT, norepinephrine, and dopamine reuptake inhibitor with antidepressant-like properties, however future studies should be performed to complete the pharmacological profiling of this compound.<\/jats:p>","DOI":"10.3390\/molecules24234218","type":"journal-article","created":{"date-parts":[[2019,11,20]],"date-time":"2019-11-20T11:06:03Z","timestamp":1574247963000},"page":"4218","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Electrophysiology and Behavioral Assessment of the New Molecule SMe1EC2M3 as a Representative of the Future Class of Triple Reuptake Inhibitors"],"prefix":"10.3390","volume":"24","author":[{"given":"Romana","family":"Koprdova","sequence":"first","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Csatlosova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Durisova","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Center of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eszter","family":"Bogi","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-3276","authenticated-orcid":false,"given":"Magdalena","family":"Majekova","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8103-8577","authenticated-orcid":false,"given":"Eliyahu","family":"Dremencov","sequence":"additional","affiliation":[{"name":"Institute of Molecular Physiology and Genetics, Center of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 840 05 Bratislava, Slovakia"},{"name":"Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 845 05 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mojmir","family":"Mach","sequence":"additional","affiliation":[{"name":"Institute of Experimental Pharmacology and Toxicology, Centre of Experimental Medicine of the Slovak Academy of Sciences, D\u00fabravsk\u00e1 cesta 9, 841 04 Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1177\/1403494811424611","article-title":"Increasing prevalence of depression from 2000 to 2006","volume":"39","author":"Andersen","year":"2011","journal-title":"Scand J. 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