{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T18:39:04Z","timestamp":1761935944989,"version":"build-2065373602"},"reference-count":34,"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":2950,"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":[[2001,1]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The N\u2010substituent of IQB\u20109302 has the same number of carbons as bupivacaine, but it exhibits a different spatial localization (n\u2010butyl <jats:italic>vs<\/jats:italic> cyclopropylmethyl). Thus, the study of the effects of IQB\u20109302 enantiomers on hKv1.5 channels will lead to a better knowledge of the determinants of stereoselective block.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effects of the IQB\u20109302 enantiomers were studied on hKv1.5 channels stably expressed in <jats:italic>Ltk<\/jats:italic><jats:sup>\u2212<\/jats:sup> cells using the whole\u2010cell configuration of the patch\u2010clamp technique. Drug molecular modelling was performed using Hyperchem software.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Block induced by IQB\u20109302 was stereoselective with the R(+) enantiomer being 3.2\u2010fold more potent than the S(\u2212) one (<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub> of 17.8\u00b10.5\u2003\u03bc<jats:sc>M<\/jats:sc> <jats:italic>vs<\/jats:italic> 58.6\u00b14.0\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>S(\u2212)\u2010 and R(+)IQB\u20109302 induced\u2010block was time\u2010 and voltage\u2010dependent consistent with an electrical distance from the cytoplasmic side of 0.173\u00b10.022 (<jats:italic>n<\/jats:italic>=12) and 0.181\u00b10.018 (<jats:italic>n<\/jats:italic>=10), respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Potency of block of pipecoloxylidide local anaesthetics was linearly related to the length between the cationic tertiary amine and the end of the substituent.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Molecular modelling shows that only when S(\u2212) and R(+) enantiomers are superimposed by their aromatic ring, their N\u2010substituents are in opposite directions, which can explain the stereospecific block induced by bupivacaine and IQB\u20109302 with hKv1.5 channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results suggest that: (a) IQB\u20109302 enantiomers block the open state of hKv1.5 channels, and (b) the length of the N\u2010substituent in these local anaesthetics and not its volume determines the potency and degree of their stereoselective hKv1.5 channel block.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>132<\/jats:bold>, 385\u2013392; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703844\">10.1038\/sj.bjp.0703844<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703844","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:09:20Z","timestamp":1106946560000},"page":"385-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Stereoselective effects of the enantiomers of a new local anaesthetic, IQB\u20109302, on a human cardiac potassium channel (Kv1.5)"],"prefix":"10.1111","volume":"132","author":[{"given":"T","family":"Gonz\u00e1lez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Longobardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Caballero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Delp\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J V","family":"Sinisterra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Tamargo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Valenzuela","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":"10.1111\/j.1600-0773.1972.tb00683.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.58.4.413"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.2.379"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(99)00942-4"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/35002099"},{"key":"e_1_2_7_7_1","first-page":"H142","article-title":"Two types of transient outward currents in adult human atrial cells","volume":"252","author":"ESCANDE D.","year":"1987","journal-title":"Am. 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