{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:46:37Z","timestamp":1790732797826,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2069,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The alkylamine drug orphenadrine (ORPH) is an inducer and inhibitor of the microsomal cytochrome <jats:italic>P<\/jats:italic>450 (CYP) system in mammals. This study evaluated the selectivity of CYP induction by ORPH in rat liver.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Immunoblot analysis indicated that ORPH was a selective inducer of the phenobarbitone (PB)\u2010inducible CYP2B in rat liver. CYP2B protein was increased to \u223c14\u2010fold of levels in untreated rat liver. By comparison PB increased CYP2B expression 40\u2010fold. Corresponding increases in the activity of CYP2B\u2010dependent androstenedione 16<jats:italic>\u03b2<\/jats:italic>\u2010hydroxylation were measured in microsomes from ORPH and PB\u2010induced rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Northern analysis indicated that CYP2B1\/2 mRNA was increased in ORPH\u2010induced rat liver. Consistent with this finding, ORPH was found to activate a PB\u2010responsive enhancer module in constitutive androstane receptor (CAR)\u2010transfected Hep G2 cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Other alkylamines like troleandomycin impair CYP turnover. We tested whether ORPH induction of CYP2B may include a post\u2010translational component. In PB\u2010pretreated animals ORPH administration delayed the loss of CYP2B after PB withdrawal, but no evidence for altered turnover was found.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These studies establish ORPH as a selective inducer of CYP2B in rat liver. Induction appears to be mediated pretranslationally by CAR activation of CYP2B gene transcription. Post\u2010translational stabilisation by an ORPH metabolite does not elicit induction. Induction of CYP2B may influence pharmacokinetic interactions involving ORPH.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>139<\/jats:bold>, 787\u2013796. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705305\">10.1038\/sj.bjp.0705305<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705305","type":"journal-article","created":{"date-parts":[[2003,6,17]],"date-time":"2003-06-17T17:29:33Z","timestamp":1055870973000},"page":"787-796","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Upregulation of cytochromes <i>P<\/i>450 2B in rat liver by orphenadrine"],"prefix":"10.1111","volume":"139","author":[{"given":"Michael","family":"Murray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Fiala\u2010Beer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan","family":"Sutton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"31","article-title":"Combination therapy with haloperidol and ORPH in schizophrenia. 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