{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:35:47Z","timestamp":1790472947612,"version":"4.1.0"},"reference-count":30,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T00:00:00Z","timestamp":1471564800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:p>\n                    Diphenhydramine, a sedative histamine H\n                    <jats:sub>1<\/jats:sub>\n                    -receptor (H\n                    <jats:sub>1<\/jats:sub>\n                    R) antagonist, was evaluated as a probe to measure drug\/H\n                    <jats:sup>+<\/jats:sup>\n                    -antiporter function at the blood\u2013brain barrier. In situ brain perfusion experiments in mice and rats showed that diphenhydramine transport at the blood\u2013brain barrier was saturable, following Michaelis\u2013Menten kinetics with a K\n                    <jats:sub>m<\/jats:sub>\n                    \u2009=\u20092.99\u2009mM and V\n                    <jats:sub>max<\/jats:sub>\n                    \u2009=\u2009179.5\u2009nmol\u2009s\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u2009g\n                    <jats:sup>\u22121<\/jats:sup>\n                    . In the pharmacological plasma concentration range the carrier-mediated component accounted for 77% of diphenhydramine influx while passive diffusion accounted for only 23%. [\n                    <jats:sup>14<\/jats:sup>\n                    C]Diphenhydramine blood\u2013brain barrier transport was proton and clonidine sensitive but was influenced by neither tetraethylammonium, a MATE1 (SLC47A1), and OCT\/OCTN (SLC22A1-5) modulator, nor P-gp\/Bcrp (ABCB\n                    <jats:sub>1a\/1b<\/jats:sub>\n                    \/ABCG2) deficiency. Brain and plasma kinetics of [\n                    <jats:sup>11<\/jats:sup>\n                    C]diphenhydramine were measured by positron emission tomography imaging in rats. [\n                    <jats:sup>11<\/jats:sup>\n                    C]Diphenhydramine kinetics in different brain regions were not influenced by displacement with 1\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    unlabeled diphenhydramine, indicating the specificity of the brain positron emission tomography signal for blood\u2013brain barrier transport activity over binding to any central nervous system target in\u00a0vivo. [\n                    <jats:sup>11<\/jats:sup>\n                    C]Diphenhydramine radiometabolites were not detected in the brain 15\u2009min after injection, allowing for the reliable calculation of [\n                    <jats:sup>11<\/jats:sup>\n                    C]diphenhydramine brain uptake clearance (Cl\n                    <jats:sub>up<\/jats:sub>\n                    \u2009=\u20090.99\u2009\u00b1\u20090.18\u2009mL\u2009min\n                    <jats:sup>\u22121\u2009<\/jats:sup>\n                    cm\n                    <jats:sup>\u22123<\/jats:sup>\n                    ). Diphenhydramine is a selective and specific H\n                    <jats:sup>+<\/jats:sup>\n                    -antiporter substrate. [\n                    <jats:sup>11<\/jats:sup>\n                    C]Diphenhydramine positron emission tomography imaging offers a reliable and noninvasive method to evaluate H\n                    <jats:sup>+<\/jats:sup>\n                    -antiporter function at the blood\u2013brain barrier.\n                  <\/jats:p>","DOI":"10.1177\/0271678x16662042","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T21:49:32Z","timestamp":1470260972000},"page":"2185-2195","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Diphenhydramine as a selective probe to study H\n                    <sup>+<\/sup>\n                    -antiporter function at the blood\u2013brain barrier: Application to [\n                    <sup>11<\/sup>\n                    C]diphenhydramine positron emission tomography imaging"],"prefix":"10.1177","volume":"37","author":[{"given":"Sylvain","family":"Auvity","sequence":"first","affiliation":[{"name":"Imagerie Mol\u00e9culaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Universit\u00e9 Paris Saclay, CEA-SHFJ, Orsay, France"},{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. Universit\u00e9 Paris Diderot, UMR-S 1144, Paris, F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Chapy","sequence":"additional","affiliation":[{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. Universit\u00e9 Paris Diderot, UMR-S 1144, Paris, F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Goutal","sequence":"additional","affiliation":[{"name":"Imagerie Mol\u00e9culaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Universit\u00e9 Paris Saclay, CEA-SHFJ, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabien","family":"Caill\u00e9","sequence":"additional","affiliation":[{"name":"Imagerie Mol\u00e9culaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Universit\u00e9 Paris Saclay, CEA-SHFJ, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Hosten","sequence":"additional","affiliation":[{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. Universit\u00e9 Paris Diderot, UMR-S 1144, Paris, F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. Universit\u00e9 Paris Diderot, UMR-S 1144, Paris, F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Decl\u00e8ves","sequence":"additional","affiliation":[{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. Universit\u00e9 Paris Diderot, UMR-S 1144, Paris, F-75013, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Tournier","sequence":"additional","affiliation":[{"name":"Imagerie Mol\u00e9culaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Universit\u00e9 Paris Saclay, CEA-SHFJ, Orsay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Cisternino","sequence":"additional","affiliation":[{"name":"Imagerie Mol\u00e9culaire In Vivo, IMIV, CEA, Inserm, CNRS, Univ. Paris-Sud, Universit\u00e9 Paris Saclay, CEA-SHFJ, Orsay, France"},{"name":"Variabilit\u00e9 de r\u00e9ponse aux psychotropes, INSERM, U1144, Paris, France; Universit\u00e9 Paris Descartes, Facult\u00e9 de pharmacie, UMR-S 1144, Paris, F-75006, France. 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