{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:03:48Z","timestamp":1784174628456,"version":"3.55.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T00:00:00Z","timestamp":1395100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T00:00:00Z","timestamp":1395100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n The prevalence of concurrent use of two or more drugs that block human ether\u2010a\u2010go\u2010go\u2010related gene product (\n hERG<\/jats:styled-content>\n ) K\n +<\/jats:sup>\n channels is not uncommon, but is not well characterized. This study defined the effects of concurrent exposure of two\n hERG<\/jats:styled-content>\n \u2010blocking drugs on\n hERG<\/jats:styled-content>\n current amplitude. Experiments were conducted to determine if concomitant exposure to two potent pore\n hERG<\/jats:styled-content>\n blockers, thioridazine and terfenadine and a weak\n hERG<\/jats:styled-content>\n blocker, erythromycin, would result in an additive, synergistic or inhibitory effect.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n hERG<\/jats:styled-content>\n currents from stably transfected\n HEK<\/jats:styled-content>\n cells were measured using the whole\u2010cell variant of the patch\u2010clamp method at physiological temperatures. Concentration\u2013response relationships for thioridazine or terfenadine were obtained with cells pre\u2010exposed to erythromycin.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n Pre\u2010exposure of cells to erythromycin resulted in an approximately 14\u201322\u2010fold rightward shift in the\n hERG<\/jats:styled-content>\n concentration\u2013response curve for thioridazine and terfenadine respectively. This reduction in affinity was not the result of a change in the voltage\u2010dependent characteristics of the channel. Results suggest an external binding site for erythromycin.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Implications<\/jats:title>\n \n Pretreatment with erythromycin induced an approximately 14\u201322\u2010fold reduction in\n hERG<\/jats:styled-content>\n affinity for pore\u2010binding drugs at concentrations of erythromycin, which by themselves only block\n hERG<\/jats:styled-content>\n by 10% or less. These results suggest distinct, allosterically linked binding sites on opposite sides of the\n hERG<\/jats:styled-content>\n channel. Occupancy of the external site by erythromycin reduces the affinity of the pore binding site. Furthermore, these results suggest that co\u2010administration of erythromycin may provide some reduction in cardiac liability of potent\n hERG\u2010blocking<\/jats:styled-content>\n drugs.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12575","type":"journal-article","created":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T21:02:53Z","timestamp":1389646973000},"page":"1668-1675","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Allosteric effects of erythromycin pretreatment on thioridazine block of\n hERG<\/scp>\n potassium channels"],"prefix":"10.1111","volume":"171","author":[{"suffix":"Jr","given":"W J","family":"Crumb","sequence":"first","affiliation":[{"name":"Zenas Technologies LLC New Orleans LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12447"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.58.3.10"},{"key":"e_1_2_9_4_1","first-page":"1","article-title":"Patch\u2010clamping human cardiac ion channels for evaluating cardiac electrophysiological effects of drugs","volume":"10","author":"Crumb W","year":"2002","journal-title":"Curr Protoc Pharmacol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-0070-7"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(02)01455-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.01.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.2.427"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq011"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22437"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.08102FP"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1155"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.039"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705336"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1027309703313"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00530.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr060368g"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(03)70028-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.9.989"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.12575","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12575","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.12575","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.12575","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T03:20:14Z","timestamp":1784172014000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.12575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,18]]},"references-count":18,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1111\/bph.12575"],"URL":"https:\/\/doi.org\/10.1111\/bph.12575","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,18]]},"assertion":[{"value":"2013-10-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-12-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}