{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T23:32:50Z","timestamp":1776468770145,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2100,"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":[[2003,5]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The mode of Ca<jats:sup>2+<\/jats:sup> channel blocking by gabapentin [1\u2010(aminomethyl)cyclohexane acetic acid] was compared to those of other Ca<jats:sup>2+<\/jats:sup> channel blockers, and the potential role of Ca<jats:sup>2+<\/jats:sup> channel antagonists in providing protection against hypoxic injury was subsequently investigated in rat cerebrocortical slices.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>mRNA for the <jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub><jats:italic>\u03b4<\/jats:italic> subunits of Ca<jats:sup>2+<\/jats:sup> channels was found in rat cerebral cortex.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Nitric oxide (NO) synthesis estimated from cGMP formation was enhanced by KCl stimulation, which was mediated primarily by the activation of N\u2010 and P\/Q\u2010type Ca<jats:sup>2+<\/jats:sup> channels. Gabapentin blocked both types of Ca<jats:sup>2+<\/jats:sup> channels, and preferentially reversed the response to 30 m<jats:sc>M<\/jats:sc> K<jats:sup>+<\/jats:sup> stimulation compared with 50 m<jats:sc>M<\/jats:sc> K<jats:sup>+<\/jats:sup> stimulation. In contrast, verapamil preferentially inhibited the response to depolarization by the higher concentration (50 m<jats:sc>M<\/jats:sc>) of K<jats:sup>+<\/jats:sup>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Gabapentin inhibited KCl\u2010induced elevation of intracellular Ca<jats:sup>2+<\/jats:sup> in primary neuronal culture.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hypoxic injury was induced in cerebrocortical slices by oxygen deprivation in the absence (severe injury) or presence of 3 m<jats:sc>M<\/jats:sc> glucose (mild injury). Gabapentin preferentially inhibited mild injury, while verapamil suppressed only severe injury. <jats:italic>\u03c9<\/jats:italic>\u2010Conotoxin GVIA (<jats:italic>\u03c9<\/jats:italic>\u2010CTX) and <jats:italic>\u03c9<\/jats:italic>\u2010agatoxin IVA (<jats:italic>\u03c9<\/jats:italic>\u2010Aga) were effective in both models.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NO synthesis was enhanced in a manner dependent on the severity of hypoxic insults. Gabapentin reversed the NO synthesis induced by mild insults, while verapamil inhibited that elicited by severe insults. <jats:italic>\u03c9<\/jats:italic>\u2010CTX and <jats:italic>\u03c9<\/jats:italic>\u2010Aga were effective in both the cases.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Therefore, the data suggest that gabapentin and verapamil cause activity\u2010dependent Ca<jats:sup>2+<\/jats:sup> channel blocking by different mechanisms, which are associated with their cerebroprotective actions and are dependent on the severity of hypoxic insults.<\/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>, 435\u2013443. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705246\">10.1038\/sj.bjp.0705246<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705246","type":"journal-article","created":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T20:21:00Z","timestamp":1054066860000},"page":"435-443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A comparison of Ca<sup>2+<\/sup> channel blocking mode between gabapentin and verapamil: implication for protection against hypoxic injury in rat cerebrocortical slices"],"prefix":"10.1111","volume":"139","author":[{"given":"Michiko","family":"Oka","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Itoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Wada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00975-X"},{"key":"e_1_2_7_3_1","first-page":"727","article-title":"Differential effect of gabapentin on neuronal and muscle calcium currents","volume":"297","author":"ALDEN K.J.","year":"2001","journal-title":"J. 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