{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:18:56Z","timestamp":1783426736739,"version":"3.54.6"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T00:00:00Z","timestamp":1348444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chirality"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Tetrahydropalmatine (THP), with one chiral center, is an alkaloid that possesses analgesic and many other pharmacological actives. The aim of the present study is to investigate stereoselective metabolism of THP enantiomers in human liver microsomes (HLM) and elucidate which cytochrome P450 (CYP) isoforms contribute to the stereoselective metabolism in HLM. Additionally, the inhibitions of THP enantiomers on activity of CYP enzymes are also investigated. The results demonstrated that (+)\u2010THP was preferentially metabolized by HLM. Ketoconazole (inhibitor of CYP3A4\/5) inhibited metabolism of (\u2212)\u2010THP or (+)\u2010THP at same degree, whereas the inhibition of fluvoxamine (inhibitor of CYP1A2) on metabolism of (+)\u2010THP was greater than that of (\u2212)\u2010THP; moreover, the metabolic rate of (+)\u2010THP was 5.3\u2010fold of (\u2212)\u2010THP in recombinant human CYP1A2. Meanwhile, THP enantiomers did not show obvious inhibitory effect on the activity of various CYP isoforms (CYP1A2, 2A6, 2C8, 2C9, 2C19, 2E1, and 3A4\/5), whereas (\u2212)\u2010THP, but not (+)\u2010THP, significantly inhibited the activity of CYP2D6 with the <jats:italic>K<\/jats:italic>i value of 6.42\u2009\u00b1\u20090.38\u2009\u03bcM. The results suggested that THP enantiomers were predominantly metabolized by CYP3A4\/5 and CYP1A2 in HLM, and (+)\u2010THP was preferentially metabolized by CYP1A2, whereas CYP3A4\/5 contributed equally to metabolism of (\u2212)\u2010THP or (+)\u2010THP. Besides, the inhibition of CYP2D6 by (\u2212)\u2010THP may cause drug\u2013drug interaction, which should be considered. <jats:italic>Chirality 25:43\u201347, 2013<\/jats:italic>. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/chir.22110","type":"journal-article","created":{"date-parts":[[2012,9,24]],"date-time":"2012-09-24T07:47:32Z","timestamp":1348472852000},"page":"43-47","source":"Crossref","is-referenced-by-count":29,"title":["Stereoselective Interaction Between Tetrahydropalmatine Enantiomers and CYP Enzymes in Human Liver Microsomes"],"prefix":"10.1002","volume":"25","author":[{"given":"Si\u2010Yuan","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui\u2010Di","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences Zhejiang University  Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00108-8"},{"key":"e_1_2_5_3_1","first-page":"318","article-title":"Pharmacological study of tetrahydropalmatine and its analogs\u2014a new type of central depressants","volume":"139","author":"Hsu B","year":"1962","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1875"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.1996.tb01769.x"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(99)00642-6"},{"key":"e_1_2_5_7_1","first-page":"1054","article-title":"Effects of tetrahydropalmatine enantiomers on dopamine receptor subtypes in brain","volume":"29","author":"Jin GZ","year":"1986","journal-title":"Sci Sin B"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-119"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.22020"},{"key":"e_1_2_5_10_1","first-page":"33","article-title":"Inhibitory and inductive effects of (\u2212)\u2010and (+)\u2010tetrahydropalmatine on CYP450 in mice","volume":"40","author":"Zhao M","year":"2011","journal-title":"Zhejiang Da Xue Xue Bao Yi Xue Ban"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(97)00068-9"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3554"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2002.tb00186.x"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm958"},{"key":"e_1_2_5_15_1","unstructured":"FlockhartD.Drug interactions: cytochrome P450 drug interaction table. 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