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Part of the relaxant action of nimesulide may be <jats:italic>via<\/jats:italic> block of myometrial Ca<jats:sup>2+<\/jats:sup> channels. Here, we describe the Ca<jats:sup>2+<\/jats:sup> channel blocking properties of nimesulide in freshly dispersed human term\u2010pregnant myometrial smooth muscle cells (HMSMCs).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Both L\u2010 and T\u2010components of the whole cell Ca<jats:sup>2+<\/jats:sup> channel current were inhibited by 100\u2003\u03bc<jats:sc>M<\/jats:sc> nimesulide (38\u00b13 and 35\u00b11% block, respectively). At physiological pH inside and outside the cell (pH<jats:sub>o<\/jats:sub>\/pH<jats:sub>i<\/jats:sub>=7.4\/7.2), this block did not depend on the holding or test potential, although a degree of use\u2010dependence was observed during high frequency stimulation at a higher concentration of drug (300\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>At pH<jats:sub>o<\/jats:sub>\/pH<jats:sub>i<\/jats:sub>=6.8, under which condition the concentration of the non\u2010ionized form of the drug is increased 3 fold compared to pH 7.4, nimesulide blocked the L\u2010type current more potently (58\u00b13% inhibition at 100\u2003\u03bc<jats:sc>M<\/jats:sc>, <jats:italic>P<\/jats:italic>&lt;0.01) compared to physiological pH. Nimesulide caused a 7\u2003mV leftward shift in the availability curve of the current at pH 6.8, suggesting that the affinity of the drug for the inactivated channel is approximately 4 fold higher than its affinity for the closed channel. We speculate that acidification and depolarization of the myometrium during the intense and prolonged contractions of labour might increase the potency of nimesulide as a Ca<jats:sup>2+<\/jats:sup> channel antagonist, promoting its action as a tocolytic agent.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 1470\u20131478; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702685\">10.1038\/sj.bjp.0702685<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702685","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:17:07Z","timestamp":1106943427000},"page":"1470-1478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Calcium antagonistic properties of the cyclooxygenase\u20102 inhibitor nimesulide in human myometrial myocytes"],"prefix":"10.1111","volume":"127","author":[{"given":"Gregory A","family":"Knock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip I","family":"Aaronson","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":"10.1161\/01.RES.59.2.229"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/S0002-9378(16)34051-0","article-title":"Maternal acid\u2010base metabolism in normal human parturition","volume":"107","author":"COHEN A.V.","year":"1970","journal-title":"Am. 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