{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T03:28:48Z","timestamp":1772249328778,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T00:00:00Z","timestamp":1439337600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012688","name":"University of Rostock","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012688","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Phenytoin is widely used as a second\u2010line treatment for status epilepticus. Besides its well\u2010known cardiac pro\u2010arrhythmogenicity, side effects on other organ systems have received less attention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study investigates the effects of phenytoin on gastrointestinal tissue function using an<jats:italic>in\u00a0vitro<\/jats:italic>model of smooth muscle preparations from rats by combining registrations of pharmacological effects on mechanical contractions, electric field potentials, and dynamic intravital fluorescence microscopy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>When added to the bathing solution at a concentration of 30\u00a0<jats:italic>\u03bc<\/jats:italic>M, phenytoin reduced the frequency of spontaneous activity significantly in antrum and portal vein preparations to 72.2\u00a0\u00b1\u00a036.5% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.022) and 80.7\u00a0\u00b1\u00a024.4% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.037) of control values, respectively. At a concentration of 100\u00a0<jats:italic>\u03bc<\/jats:italic>M, the\u00a0height of spontaneous contractions declined to 9.8\u00a0\u00b1\u00a019.6% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.005) (antrum), 15.7\u00a0\u00b1\u00a028.2% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.004) (portal vein), and 31.8\u00a0\u00b1\u00a031.3% (<jats:italic>p<\/jats:italic>\u00a0= 0.005) (colon) in comparison to the control conditions before the application of phenytoin. Depolarization triggered increases in calcium dependent fluorescence signals were reduced by 52.8\u00a0\u00b1\u00a039.1% (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.012) The inhibition of spontaneous activity caused by phenytoin was reduced in the presence of the L\u2010type calcium channel agonist<jats:styled-content style=\"fixed-case\">BAY<\/jats:styled-content>K8644(\u2010).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Phenytoin exerts strong inhibitory effects on the spontaneous and stimulated contractile activity of smooth muscles from both the upper and lower gastrointestinal tract. The mechanism underlying this\u00a0effect is not related to the sodium channel blocking activity of phenytoin, but is rather caused\u00a0by an inhibition of calcium entry through voltage dependent L\u2010type calcium channels. The results of this study should raise vigilance to gastrointestinal complications in patients treated with phenytoin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12645","type":"journal-article","created":{"date-parts":[[2015,8,12]],"date-time":"2015-08-12T08:50:51Z","timestamp":1439369451000},"page":"1453-1465","source":"Crossref","is-referenced-by-count":13,"title":["Phenytoin inhibits contractions of rat gastrointestinal and portal vein smooth muscle by inhibiting calcium entry"],"prefix":"10.1111","volume":"27","author":[{"given":"R.","family":"Patejdl","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4tsmedizin Rostock Rostock Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.\u2010C.","family":"Leroux","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4tsmedizin Rostock Rostock Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Noack","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Physiologie Universit\u00e4tsmedizin Rostock Rostock Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4081\/ni.2012.e17"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.7.1070"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.01101.x"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2009.02917.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-012-9711-3"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2014.06.008"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-3623(96)00062-6"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.12.011"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31824e14c1"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-007-0942-2"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0148607114526450"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2012.12.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00592289"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867320666131119151136"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0029(19991115)47:4<239::AID-JEMT3>3.0.CO;2-0"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.61.1.85"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-90-21972"},{"key":"e_1_2_11_19_1","first-page":"101","article-title":"Effects of diphenylhydantoin on smooth muscle","volume":"203","author":"Ferrari M","year":"1973","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.5414\/TEP27202"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.1077"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1966.tb01668.x"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1967.sp008169"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00171341"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1998.00464.x"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.5414\/TEP22248"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1059-1311(05)80205-5"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1998.tb01387.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13547.x"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0022-3565(25)21001-1","article-title":"Mechanisms of calcium channel block by phenytoin","volume":"246","author":"Twombly DA","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018384"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2008.01561.x"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198810010-00014"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199019050-00001"},{"key":"e_1_2_11_35_1","first-page":"518","article-title":"Effects of phenytoin on vection\u2010induced motion sickness and gastric myoelectric activity","volume":"65","author":"Stern RM","year":"1994","journal-title":"Aviat Space Environ Med"}],"container-title":["Neurogastroenterology &amp; 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