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Concentration dependency was studied for the stimulatory\/inhibitory effects of phenothiazines on MPP+ transport.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key findings<\/jats:title><jats:p>Among the 11 phenothiazines examined, the majority were found to have comparable effects on transporter function between the orthologous forms, while three phenothiazines, particularly mesoridazine, had complex impacts on transporter function. For rOCT2, mesoridazine stimulated transport at 0.1 and 1 \u03bcmMPP+ with the mesoridazine concentration\u2013uptake curve becoming bell-shaped. This conditional effect became less pronounced at 30 \u03bcmMPP+, resulting in an inhibition curve with a typical profile. For hOCT2, mesoridazine behaved as a typical inhibitor of transporter function at all MPP+ concentrations, although the kinetics of inhibition were still affected by the substrate concentration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The conditional stimulation by mesoridazine in rOCT2, and the lack thereof in hOCT2, may be a manifestation of the interaction of phenothiazine with substrate binding at the high-affinity site of the OCT2. As OCT2 was previously indicated in some drug\u2013drug interactions, the conditional stimulation of OCT2 and its potential species-differences may be of practical relevance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jphp.12799","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T10:12:42Z","timestamp":1502791962000},"page":"1513-1523","source":"Crossref","is-referenced-by-count":3,"title":["The conditional stimulation of rat organic cation transporter 2, but not its human ortholog, by mesoridazine: the possibility of the involvement of the high-affinity binding site of the transporter in the stimulation"],"prefix":"10.1093","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6967-5271","authenticated-orcid":false,"given":"Sungwoo","family":"Hyung","sequence":"first","affiliation":[{"name":"College of Pharmacy, Seoul National University , Gwanak-gu, Seoul,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonji","family":"Pyeon","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University , Gwanak-gu, Seoul,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Eun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University , Gwanak-gu, Seoul,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoo-Kyung","family":"Song","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University , Gwanak-gu, Seoul,","place":["Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suk-Jae","family":"Chung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Seoul National University , Gwanak-gu, Seoul,","place":["Korea"]},{"name":"Research Institute of Pharmaceutical Sciences, College of Pharmacy, 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