{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:53:25Z","timestamp":1789678405348,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":3260,"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":[[2000,3]]},"abstract":"<jats:p>\n                    <jats:list list-type=\"explicit-label\">\n                      <jats:list-item>\n                        <jats:p>The cardiotoxic effects of fenfluramine hydrochloride on mechanical and electrical activity were studied in papillary muscles, Purkinje fibres, left atria and ventricular myocytes of guinea\u2010pigs.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Force of contraction (f\n                          <jats:sub>c<\/jats:sub>\n                          ) was measured isometrically, action potentials and maximum rate of rise of the action potential (V\n                          <jats:sub>max<\/jats:sub>\n                          ) were recorded by means of the intracellular microelectrode technique and the sodium current (I\n                          <jats:sub>Na<\/jats:sub>\n                          ) with patch\u2010clamp technique in the cell\u2010attached mode. For kinetic analysis (S)\u2010DPI\u2010201\u2010106\u2010modified Na\n                          <jats:sup>+<\/jats:sup>\n                          channels from isolated guinea\u2010pig ventricular heart cells were used.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Fenfluramine (1\u2013300\u2003\u03bc\n                          <jats:sc>M<\/jats:sc>\n                          ) produced negative chronotropic and inotropic effects; additional extracellular Ca\n                          <jats:sup>2+<\/jats:sup>\n                          competitively antagonized the negative inotropic effect.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          Fenfluramine concentration\u2010dependently reduced V\n                          <jats:sub>max<\/jats:sub>\n                          and showed tonic blockade of sodium channels, shortened the action potential duration in papillary muscles and Purkinje fibres.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          In cell\u2010attached patches, fenfluramine decreased I\n                          <jats:sub>Na<\/jats:sub>\n                          concentration\u2010dependently (10\u2013100\u2003\u03bc\n                          <jats:sc>M<\/jats:sc>\n                          ), frequency\u2010independently (0.1\u20133\u2003Hz; 30\u2003\u03bc\n                          <jats:sc>M<\/jats:sc>\n                          ). The h\n                          <jats:sub>\u221e<\/jats:sub>\n                          curve was shifted towards hyperpolarizing direction. At 30\u2003\u03bc\n                          <jats:sc>M<\/jats:sc>\n                          , fenfluramine blocked the sodium channel at all test potentials to the same degree, and neither changed the threshold and reversal potentials nor the peak of the curve.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>No effect on single channel availability, but a significant decrease in mean open times and increase in mean closed times was observed.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Mean duration of the bursts decreased and number of openings per record increased with increasing drug concentration.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          It is concluded that the effect on I\n                          <jats:sub>Na<\/jats:sub>\n                          plays an important role in the cardiotoxicity of fenfluramine in addition to primary pulmonary hypertension and valvular disorders.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                    (2000)\n                    <jats:bold>129<\/jats:bold>\n                    , 843\u2013852; doi:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703118\">10.1038\/sj.bjp.0703118<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1038\/sj.bjp.0703118","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T15:46:58Z","timestamp":1106927218000},"page":"843-852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cardiotoxic effects of fenfluramine hydrochloride on isolated cardiac preparations and ventricular myocytes of guinea\u2010pigs"],"prefix":"10.1111","volume":"129","author":[{"given":"Sridharan","family":"Rajamani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Studenik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Lemmens\u2010Gruber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Heistracher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1056\/NEJM199608293350901","article-title":"Appetite\u2010suppressant drugs and the risk of primary pulmonary hypertension","volume":"335","author":"ABENHAIM L.","year":"1996","journal-title":"N. Eng. J. Med."},{"key":"e_1_2_7_3_1","first-page":"503","article-title":"Sodium channels in cultured cardiac cells","volume":"415","author":"CACHELIN A.B.","year":"1983","journal-title":"J. Physiol."},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708283370912"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.63.1.50"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6107(98)00002-9"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.54.6.636"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708283370901"},{"key":"e_1_2_7_9_1","first-page":"F16","volume-title":"Therapeutic drugs","author":"DOLLERY C.","year":"1991"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1971.tb09935.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1984.sp015483"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1994.tb03738.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019903"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199708283370911"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.55.4.427"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1989.tb11921.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018498"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00656997"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01003037"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)80156-9"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.69.4.497"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.24.040184.002131"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/1043-6618(90)90735-V"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.6098.1322"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391102"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391101"},{"key":"e_1_2_7_27_1","first-page":"H163","article-title":"Negative shift of cardiac Na+ channels by DPI 201\u2010106","volume":"89","author":"KIMITSUKI T.","year":"1990","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(87)83182-X"},{"key":"e_1_2_7_29_1","first-page":"A725","article-title":"Anorexic agents inhibit potassium current in pulmonary artery smooth muscle cells","volume":"151","author":"MICHELAKIS E.D.","year":"1995","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"e_1_2_7_30_1","first-page":"H1056","article-title":"A uniform enzymatic method for dissociation of myocytes from heart and stomachs of vertebrates","volume":"249","author":"MITRA R.","year":"1985","journal-title":"Am. J. Physiol."},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.6053.70"},{"key":"e_1_2_7_32_1","first-page":"1249","article-title":"Evaluation of inotropically active drugs on isolated papillary muscle","volume":"17","author":"REITER M.","year":"1967","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_7_33_1","first-page":"1273","volume-title":"Textbook of Pulmonary diseases","author":"ROUNDS S.","year":"1998"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(86)90011-0"},{"key":"e_1_2_7_35_1","unstructured":"US DEPARTMENT OF HEALTH AND HUMAN SERVICES. (1997).Morbidity Mortality Weekly Report. 46 1061\u20131066."},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(75)80086-2"},{"key":"e_1_2_7_37_1","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1001\/jama.1994.03520140017007","article-title":"Obesity drug renews toxicity debate","volume":"272","author":"VOELKER R.","year":"1994","journal-title":"JAMA."},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79732-1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.9.2216"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199809103391103"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(85)83965-5"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(94)80568-5"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703118","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0703118","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0703118","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T23:48:47Z","timestamp":1695858527000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0703118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,3]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2000,3]]}},"alternative-id":["10.1038\/sj.bjp.0703118"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0703118","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,3]]},"assertion":[{"value":"2009-02-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}