{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:29:05Z","timestamp":1761560945207},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":3931,"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":[[1998,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>An enhancement of promoted release of \u03b3\u2010aminobutyric acid (GABA) and a change in GABA\u2010metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA\u2010transaminase but it also interferes with GABA\u2010release and GABA\u2010uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (<jats:italic>n<\/jats:italic>=107) of guinea\u2010pigs (<jats:italic>n<\/jats:italic>=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30\u2013600 \u03bc<jats:sc>M<\/jats:sc>; 5.1\u2013102.72 \u03bcg ml<jats:sup>\u22121<\/jats:sup>), vigabatrin (50\u2013200 \u03bc<jats:sc>M<\/jats:sc>, 6.45\u201325.8 \u03bcg ml<jats:sup>\u22121<\/jats:sup>) and the GABA<jats:sub>A<\/jats:sub>\u2010receptor antagonist bicuculline (100 \u03bc<jats:sc>M<\/jats:sc>) were added to the bath solution for 3 h.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Gabapentin, in concentrations up to 600 \u03bc<jats:sc>M<\/jats:sc>, failed to decrease the repetition rate or duration of e.f.p. (<jats:italic>n<\/jats:italic>=19). However, vigabatrin, evoked a dose\u2010dependent reduction of the repetition rate of e.f.p. For a concentration of 100 \u03bc<jats:sc>M<\/jats:sc> (12.9 \u03bcg ml<jats:sup>\u22121<\/jats:sup>) there was a reduction down to 48\u00b15% (mean\u00b1s.e.mean) of the initial value within 3 h (<jats:italic>n<\/jats:italic>=11). With simultaneous administration of vigabatrin (100 \u03bc<jats:sc>M<\/jats:sc>) and gabapentin (60 \u03bc<jats:sc>M<\/jats:sc>) for 3 h (<jats:italic>n<\/jats:italic>=15), the repetition rate of e.f.p. decreased down to 8\u00b13%, which is significantly different from the values obtained after administration of 100 \u03bc<jats:sc>M<\/jats:sc> vigabatrin alone (<jats:italic>P<\/jats:italic>&lt;0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA<jats:sub>A<\/jats:sub>\u2010receptor antagonist bicuculline (100 \u03bc<jats:sc>M<\/jats:sc>, <jats:italic>n<\/jats:italic>=16).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA\u2010release machinery is induced by vigabatrin which then can be augmented by gabapentin.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701825","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:21:10Z","timestamp":1106940070000},"page":"370-376","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an <i>in vitro<\/i> model of epilepsy"],"prefix":"10.1111","volume":"124","author":[{"given":"A","family":"L\u00fccke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U","family":"Mu\u00dfhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"K\u00f6hling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Osterfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W","family":"Sch\u00fctte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E\u2010J","family":"Speckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(80)91295-0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(96)00682-6"},{"key":"e_1_2_6_4_1","first-page":"209","volume-title":"Antiepileptic Drug Interactions","author":"Bourgeois B.F.D.","year":"1989"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(93)90026-4"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1989.sp017629"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00174-3"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015804"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(90)90757-Z"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0920-1211(95)00028-9"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1993.tb02423.x"},{"key":"e_1_2_6_12_1","first-page":"636","article-title":"Effects of gabapentin on release of gamma\u2010aminobutyric acid from slices of rat neostriatum","volume":"43","author":"G\u00f6tz E.","year":"1993","journal-title":"Arzneim. 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