{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:30:14Z","timestamp":1774423814261,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,27]],"date-time":"2019-02-27T00:00:00Z","timestamp":1551225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Methenamine (hexamethylenetetramine, hexamine, urotropine) is a compound discovered in 1859, which is still currently being used as a urinary antiseptic. Methenamine is highly soluble in water and polar solvents, and its molecular constitution is similar to adamantane compounds with tetrahedral cage like structure. In acidic conditions, methenamine decomposes to formaldehyde and ammonia. Recently, methenamine has gained a renewal of interest due to antibiotic\u2010resistant bacteria urinary tract infections; interestingly, bacteria cannot gain resistance to formaldehyde. In 1968, David and Burkitt reported remarkable regression of four Burkitt Lymphoma patients in eight subjects who were treated with septicemine (a solution containing 6.3\u00a0g of methenamine iodomethylate and 1\u00a0g of methenamine sodium benzoate in 100\u00a0cc distilled water). Unfortunately, these striking observations did not gain interest in the medical community; despite experimental models that showed that methenamine synergized with hyperthermia, radiation, and chemotherapy to block cancer growth. As the hypoxic core of tumours have an acidic <jats:styled-content style=\"fixed-case\">pH<\/jats:styled-content>, it would be plausible to expect that methenamine would selectively target dormant, non\u2010proliferative, and treatment\u2010resistant cancer clones in large tumours. Moreover, previous data suggests that methenamine can be safely used intravenously and for treatment of infections of the central nervous system. It may therefore be an effective adjuvant in treatment of systemic cancers and glioblastoma.<\/jats:p>","DOI":"10.1111\/1440-1681.13070","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T20:49:47Z","timestamp":1549399787000},"page":"407-412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Methenamine's journey of 160\u00a0years: Repurposal of an old urinary antiseptic for treatment and hypoxic radiosensitization of cancers and glioblastoma"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7804-4087","authenticated-orcid":false,"given":"Meric A.","family":"Altinoz","sequence":"first","affiliation":[{"name":"Department of Biochemistry Acibadem University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aysel","family":"Ozpinar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Acibadem University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alp","family":"Ozpinar","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u0130lhan","family":"Elmaci","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Acibadem University Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,27]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-017-1613-6"},{"issue":"2","key":"e_1_2_12_3_1","first-page":"189","article-title":"Activation of adriamycin by the pH\u2010dependent formaldehyde\u2010releasing prodrug hexamethylenetetramine","volume":"2","author":"Swift LP","year":"2003","journal-title":"Mol Cancer Ther"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/or_00000355"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2014.904202"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000224844"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.4.1.19"},{"issue":"4","key":"e_1_2_12_8_1","first-page":"193","article-title":"A note on the intravenous use of urotropine in influenza and nephritis","volume":"63","author":"Bhattacharyya AK","year":"1928","journal-title":"Ind Med Gaz"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.3121.628"},{"issue":"6","key":"e_1_2_12_10_1","first-page":"954","article-title":"Intravenous administration of urotropin for post\u2010operative urine retention","volume":"80","author":"Takats G","year":"1924","journal-title":"Ann Surg"},{"issue":"5","key":"e_1_2_12_11_1","first-page":"221","article-title":"A note on the intravenous use of urotropine","volume":"60","author":"Ghosh NN","year":"1925","journal-title":"Ind Med Gaz"},{"issue":"6","key":"e_1_2_12_12_1","first-page":"356","article-title":"Intravenous hexamine in mumps","volume":"62","author":"Das BC","year":"1927","journal-title":"Ind Med Gaz"},{"issue":"11","key":"e_1_2_12_13_1","first-page":"1411","article-title":"Effects of methenamine on mouse lymphoma cells","volume":"39","author":"Reitz M","year":"1989","journal-title":"Arzneimittelforschung"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.2909.455"},{"issue":"5","key":"e_1_2_12_15_1","first-page":"263","article-title":"A case of cerebro\u2010spinal fever successfully treated by intravenous injections of urotropine","volume":"69","author":"Chopra BL","year":"1934","journal-title":"Ind Med Gaz"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2011.11.008"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2012.12.021"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5626.288"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2018.1435540"},{"issue":"11","key":"e_1_2_12_20_1","first-page":"1369","article-title":"Prevention using ascorbic acid, hexamethylenetetramine and sodium metabisulfite of the blastomogenic effect caused by the combined administration into the stomach of mice of sodium nitrite with methylurea or with aminopyrine","volume":"34","author":"Dzhioev FK","year":"1988","journal-title":"Vopr Onkol"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr\/54190057"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm_00000027"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.09072"},{"issue":"1","key":"e_1_2_12_24_1","first-page":"61","article-title":"Whole body hyperthermia supplemented with urotropin in the treatment of malignant tumors","volume":"27","author":"Ismail\u2010Zade RS","year":"2005","journal-title":"Exp Oncol"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.08.019"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-016-5089-8"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.01.009"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06086-2"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26448"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.651679"}],"container-title":["Clinical and Experimental Pharmacology and Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13070","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/1440-1681.13070","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1440-1681.13070","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:21:08Z","timestamp":1694391668000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1440-1681.13070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,27]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1111\/1440-1681.13070"],"URL":"https:\/\/doi.org\/10.1111\/1440-1681.13070","archive":["Portico"],"relation":{},"ISSN":["0305-1870","1440-1681"],"issn-type":[{"value":"0305-1870","type":"print"},{"value":"1440-1681","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,27]]},"assertion":[{"value":"2018-09-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}