{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:35:50Z","timestamp":1781663750316,"version":"3.54.5"},"reference-count":42,"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":150,"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":[[2008,9]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Voltage\u2010operated sodium channels constitute major target sites for local anaesthetic\u2010like action. The clinical use of local anaesthetics is still limited by severe side effects, in particular, arrhythmias and convulsions. These side effects render the search for new local anaesthetics a matter of high interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>We have investigated the effects of three halogenated structural analogues of propofol on voltage\u2010operated human skeletal muscle sodium channels (Na<jats:sub>V<\/jats:sub>1.4) and the effect of one compound (4\u2010chloropropofol) on neuronal sodium channels (Na<jats:sub>V<\/jats:sub>1.2) heterologously expressed in human embryonic kidney cell line 293.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>4\u2010Iodo\u2010, 4\u2010bromo\u2010 and 4\u2010chloropropofol reversibly suppressed depolarization\u2010induced whole\u2010cell sodium inward currents with high potency. The IC<jats:sub>50<\/jats:sub>for block of resting channels at \u2212150\u2003mV was 2.3, 3.9 and 11.3\u2003\u03bc<jats:sc>M<\/jats:sc>in Na<jats:sub>V<\/jats:sub>1.4, respectively, and 29.2\u2003\u03bc<jats:sc>M<\/jats:sc>for 4\u2010chloropropofol in Na<jats:sub>V<\/jats:sub>1.2. Membrane depolarization inducing inactivation strongly increased the blocking potency of all compounds. Estimated affinities for the fast\u2010inactivated channel state were 81\u2003n<jats:sc>M<\/jats:sc>, 312\u2003n<jats:sc>M<\/jats:sc>and 227\u2003n<jats:sc>M<\/jats:sc>for 4\u2010iodopropofol, 4\u2010bromopropofol and 4\u2010chloropropofol in Na<jats:sub>V<\/jats:sub>1.4, and 450\u2003n<jats:sc>M<\/jats:sc>for 4\u2010chloropropofol in Na<jats:sub>V<\/jats:sub>1.2. Recovery from fast inactivation was prolonged in the presence of drug leading to an accumulation of block during repetitive stimulation at high frequencies (100\u2003Hz).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>Halogenated propofol analogues constitute a novel class of sodium channel\u2010blocking drugs possessing almost 100\u2010fold higher potency compared with the local anaesthetic and anti\u2010arrhythmic drug lidocaine. Preferential drug binding to inactivated channel states suggests that halogenated propofol analogues might be especially effective in suppressing ectopic discharges in a variety of pathological conditions.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>155<\/jats:bold>, 265\u2013275; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/bjp.2008.255\">10.1038\/bjp.2008.255<\/jats:ext-link>; published online 23 June 2008<\/jats:p><\/jats:sec>","DOI":"10.1038\/bjp.2008.255","type":"journal-article","created":{"date-parts":[[2008,6,23]],"date-time":"2008-06-23T16:56:27Z","timestamp":1214240187000},"page":"265-275","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["High\u2010affinity blockade of voltage\u2010operated skeletal muscle and neuronal sodium channels by halogenated propofol analogues"],"prefix":"10.1111","volume":"155","author":[{"given":"G","family":"Haeseler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Karst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Foadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Gudehus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Roeder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Hecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Dengler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Leuwer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"S1","article-title":"Guide to receptors and channels (GRAC)","volume":"153","author":"Alexander SPH","year":"2008","journal-title":"Br J Pharmacol"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2006.01.444"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021503"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.107.5.643"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.81.5.613"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.03.192"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200101000-00024"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00585952"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(92)90067-L"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1996.sp021684"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2004.07.033"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(73)90341-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704854"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003643-200303000-00007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200005000-00029"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704024"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-200105000-00021"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00293-T"},{"key":"e_1_2_9_21_1","first-page":"390","volume-title":"Ionic Channels of Excitable Membranes","author":"Hille B","year":"1992"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1959.sp006278"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0611fje"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-002-0871-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S0022-3565(24)29544-6","article-title":"General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of \u03b3\u2010aminobutyric acid (GABA) current at the GABAA receptor but not with lipid solubility","volume":"297","author":"Krasowski MD","year":"2001","journal-title":"J Pharmacol Exp Therapeut"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.44.101802.121627"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705594"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200106000-00020"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1994.sp020260"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01033-0"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1074"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702449"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp020996"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.113.1.3"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(00)00463-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.10.035"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm970681h"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.113.1.7"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79566-8"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.03.018"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.02.003"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00782-8"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81292-X"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.255","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fbjp.2008.255","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/bjp.2008.255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T20:45:22Z","timestamp":1738269922000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/bjp.2008.255"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1038\/bjp.2008.255"],"URL":"https:\/\/doi.org\/10.1038\/bjp.2008.255","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}