{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T20:05:30Z","timestamp":1790280330559,"version":"4.1.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2008,11,1]],"date-time":"2008-11-01T00:00:00Z","timestamp":1225497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Naegleria fowleri<\/jats:italic>is a ubiquitous, pathogenic free-living amoeba; it is the most virulent<jats:italic>Naegleria<\/jats:italic>species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for<jats:italic>N. fowleri<\/jats:italic>infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic<jats:italic>N. fowleri<\/jats:italic>. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When<jats:italic>N. fowleri<\/jats:italic>trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 \u03bcg\/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by<jats:italic>N. fowleri<\/jats:italic>, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg\/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against<jats:italic>N. fowleri<\/jats:italic>in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.<\/jats:p>","DOI":"10.1128\/aac.00197-08","type":"journal-article","created":{"date-parts":[[2008,9,3]],"date-time":"2008-09-03T01:11:21Z","timestamp":1220404281000},"page":"4010-4016","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":79,"title":["Effect of Therapeutic Chemical Agents In Vitro and on Experimental Meningoencephalitis Due to<i>Naegleria fowleri<\/i>"],"prefix":"10.1128","volume":"52","author":[{"given":"Jong-Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk-Yul","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Ju","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul 121-752, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daeho","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyongmin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Il","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Environmental Medical Biology, Yonsei University College of Medicine, Seoul 121-752, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Joon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, and Department of Molecular Science and Technology, Ajou University School of Medicine, Suwon 443-721"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"379","volume":"19","year":"1972","unstructured":"Anderson, K., and A. Jamieson. 1972. Primary amoebic meningoencephalitis. Lancet19:379.","journal-title":"Lancet"},{"key":"e_1_3_2_3_2","first-page":"596","volume":"7","year":"1970","unstructured":"Apley, J., S. K. Clarke, A. P. Roome, S. A. Sandry, G. Saygi, B. Silk, and D. C. Warhurst. 1970. Primary amoebic meningoencephalitis in Britain. BMJ7:596-599.","journal-title":"BMJ"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/S0022-3565(24)36687-X","volume":"281","year":"1997","unstructured":"Aubrecht, J., M. E. Goad, E. M. Simpson, and R. H. Schiestl. 1997. Expression of Hygr in transgenic mice causes resistance to toxic effects of hygromycin B in vivo. J. Pharmacol. Exp. Ther.281:992-997.","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki417"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/S0022-3565(25)04467-2","volume":"110","year":"1954","unstructured":"Brand, E. D., T. D. Harris, H. L. Borison, and L. S. Goodman. 1954. The anti-emetic activity of 10-(\u03b3-dimethylaminopropyl)-2-chlorophenothiazine (chlorpromazine) in dog and cat. J. Pharmacol. Exp. Ther.110:86-92.","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_2_7_2","first-page":"1","volume":"96","year":"1968","unstructured":"Carter, R. F. 1968. Primary amoebic meningoencephalitis: clinical, pathological, and epidemiological features of six fatal cases. J. Pathol. Bacteriol.96:1-25.","journal-title":"J. Pathol. Bacteriol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711000402"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(72)90147-2"},{"key":"e_1_3_2_10_2","first-page":"581","volume":"7","year":"1970","unstructured":"Goodman, J. S., and M. G. Koenig. 1970. Amphotericin B: specifics of administration. Mod. Treat.7:581-595.","journal-title":"Mod. Treat."},{"key":"e_1_3_2_11_2","first-page":"524","volume":"17","year":"2003","unstructured":"Goswick, S. M., and G. M. Brenner. 2003. Activities of azithromycin and amphotericin B against Naegleria fowleri in vitro and in a mouse model of primary amebic meningoencephalitis. Antimicrob. Agents Chemother.17:524-528.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.2307\/3284060","volume":"81","year":"1995","unstructured":"Gupta, S., P. K. Ghosh, G. P. Dutta, and R. A. Vishwakarma. 1995. In vivo study of artemisinin and its derivatives against primary amebic meningoencephalitis caused by Naegleria fowleri. J. Parasitol.81:1012-1013.","journal-title":"J. Parasitol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3347\/kjp.2004.42.1.35"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jgm.984","volume":"9","year":"2007","unstructured":"Kanerva, A., M. Raki, T. Ranki, M. S\u00e4rkioja, J. Koponen, R. A. Desmond, A. Helin, U. H. Stenman, H. Isoniemi, K. H\u00f6ckerstedt, A. Ristim\u00e4ki, and A. Hemminki. 2007. Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity. J. Gene Med.9:3-9.","journal-title":"J. Gene Med."},{"key":"e_1_3_2_15_2","first-page":"333","volume":"15","year":"1993","unstructured":"Loschiavo, F., T. Ventura-Spagnolo, E. Sessa, and P. Bramanti. 1993. Acute primary meningoencephalitis from entamoeba Naegleria fowleri: report of a clinical case with a favorable outcome. Acta Neurol.15:333-340.","journal-title":"Acta Neurol."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.12.4520-4527.2004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1056\/NEJM196801182780302","volume":"278","year":"1968","unstructured":"McCurdy, D. K., M. Frederic, and J. R. Elkinton. 1968. Renal tubular acidosis due to amphotericin B. N. Engl. J. Med.278:124-130.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_18_2","first-page":"112","volume":"74","year":"1991","unstructured":"Poungvarin, N., and P. Jariya. 1991. The fifth nonlethal case of primary amoebic meningoencephalitis. J. Med. Assoc. Thai.74:112-115.","journal-title":"J. Med. Assoc. Thai."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/28.suppl_B.49"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.11.3472-3477.2002"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1550-7408.2005.00082.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.25.1.109"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2004.06.004"},{"key":"e_1_3_2_24_2","first-page":"346","volume":"11","year":"1982","unstructured":"Seidel, J. S., P. Harmatz, G. S. Visvesvara, A. Cohen, J. Edwards, and J. Turner. 1982. Successful treatment of primary amebic meningoencephalitis. N. Engl. J. Med.11:346-348.","journal-title":"N. Engl. J. Med."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/143.2.193"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa021556"},{"key":"e_1_3_2_27_2","first-page":"876","volume":"86","year":"2003","unstructured":"Tiewcharoen, S., V. Junnu, and S. Suvoutho. 2003. Effect of antifungal drugs on pathogenic Naegleria spp. isolated from natural water sources. J. Med. Assoc. Thai.86:876-882.","journal-title":"J. Med. Assoc. Thai."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2004.11.003"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01177-07"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/0303-8467(93)90132-Z"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.414-421.2006"},{"key":"e_1_3_2_32_2","first-page":"701","volume":"51","year":"1971","unstructured":"Willaert, E. 1971. Isolement et culture in vitro des amibes de genre Naegleria. Ann. Soc. Belg. Med. Trop.51:701-708.","journal-title":"Ann. Soc. Belg. Med. Trop."},{"key":"e_1_3_2_33_2","first-page":"59","volume":"2","year":"1965","unstructured":"Winnie, A. P., and V. J. Collins. 1965. Clinical management of the patient in shock. Pharmacologic adjuncts to the management of shock. Clin. Anesth.2:59-77.","journal-title":"Clin. Anesth."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00197-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00197-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T20:02:04Z","timestamp":1738353724000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00197-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11]]},"references-count":32,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,11]]}},"alternative-id":["10.1128\/AAC.00197-08"],"URL":"https:\/\/doi.org\/10.1128\/aac.00197-08","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11]]},"assertion":[{"value":"2008-02-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-08-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}