{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:57:20Z","timestamp":1791518240912,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100014851","name":"Bayer Animal Health GmbH","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014851","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>The antiparasitic drug emodepside (<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>) is a substrate of the P\u2010glycoprotein multidrug efflux carrier (P\u2010gp; syn.<jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>1,<jats:styled-content style=\"fixed-case\">ABCB<\/jats:styled-content>1), which has an important function in protecting the brain from potentially toxic compounds by functional drug efflux at the blood\u2013brain barrier (<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>). Many dogs of the Collie breed and even dogs of many other breeds have a loss\u2010of\u2010function 4\u2010bp deletion mutation in the<jats:italic><jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>1<\/jats:italic>gene. In these dogs, brain penetration of many P\u2010gp\u2010transported drugs is increased and so their therapeutic usage is restricted. To elucidate the role of P\u2010gp at the<jats:styled-content style=\"fixed-case\">BBB<\/jats:styled-content>for the brain penetration of<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>, we applied<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>at 1\u00a0mg\/kg to<jats:italic>mdr1<\/jats:italic>\u2010deficient (<jats:styled-content style=\"fixed-case\">PGP<\/jats:styled-content><jats:sup>mut<\/jats:sup>) and<jats:italic>mdr1<\/jats:italic>\u2010intact (<jats:styled-content style=\"fixed-case\">PGP<jats:sup>WT<\/jats:sup><\/jats:styled-content>)<jats:styled-content style=\"fixed-case\">CF<\/jats:styled-content>1 mice. Whereas in the brain of the<jats:styled-content style=\"fixed-case\">PGP<jats:sup>WT<\/jats:sup><\/jats:styled-content>mice,<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>was below the detection level of 10\u00a0ng\/g, its concentration was at 43.7\u00a0ng\/g in the<jats:styled-content style=\"fixed-case\">PGP<\/jats:styled-content><jats:sup>mut<\/jats:sup>mice. Furthermore, appearance of neurological toxicity was analyzed in these mice after application of 1\u00a0mg\/kg<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>using a rotarod setup. In all<jats:styled-content style=\"fixed-case\">PGP<\/jats:styled-content><jats:sup>mut<\/jats:sup>mice, but not in the<jats:styled-content style=\"fixed-case\">PGP<jats:sup>WT<\/jats:sup><\/jats:styled-content>mice, the walking performance on the rotarod was impaired by<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>with clear differences in the degree and duration of neurological toxicity. Some of the mice were completely unable to walk on the rotarod already at 2\u00a0h after drug application and showed long\u2010lasting ataxia over &gt;24\u00a0h. Others even showed significantly reduced walking performance, but completely recovered within 1\u00a0day.<jats:italic>In conclusion,<\/jats:italic>P\u2010gp restricts brain penetration of<jats:styled-content style=\"fixed-case\">EMO<\/jats:styled-content>and prevents neurological toxicity of this drug in mice.<\/jats:p>","DOI":"10.1111\/jvp.12149","type":"journal-article","created":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T21:20:21Z","timestamp":1406928021000},"page":"74-79","source":"Crossref","is-referenced-by-count":22,"title":["Brain penetration of emodepside is increased in P\u2010glycoprotein\u2010deficient mice and leads to neurotoxicosis"],"prefix":"10.1111","volume":"38","author":[{"given":"S.","family":"Elmsh\u00e4user","sequence":"first","affiliation":[{"name":"Institute of Pharmacology and Toxicology Justus Liebig University of Giessen Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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