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The AChE\u2010inhibitory activity of known AChE inhibitors was quantified <jats:italic>in vitro<\/jats:italic> and their <jats:italic>in vivo<\/jats:italic> mortality\u2010reducing efficacy was compared, when given prophylactically before the exposure to the OPC diisopropylfluorophosphate (DFP). The IC<jats:sub>50<\/jats:sub> was measured <jats:italic>in vitro<\/jats:italic> for the known AChE inhibitors pyridostigmine, physostigmine, ranitidine, tiapride, tacrine, 7\u2010methoxytacrine, amiloride, metoclopramide, methylene blue and the experimental oxime K\u201027. Their <jats:italic>in vivo<\/jats:italic> efficacy, when given as pretreatment, to protect rats from DFP\u2010induced mortality was quantified by determining the relative risk of death (RR) by Cox analysis, with RR = 1 for animals given only DFP, but no pretreatment. Physostigmine was the strongest <jats:italic>in vitro<\/jats:italic> AChE\u2010inhibitor (IC<jats:sub>50<\/jats:sub> = 0.012\u2009\u00b5 <jats:sc>m<\/jats:sc>), followed by 7\u2010methoxytacrine, tacrine, pyridostigmine and methylene blue. Ranitidine (IC<jats:sub>50<\/jats:sub> = 2.5\u2009\u00b5 <jats:sc>m<\/jats:sc>), metoclopramide and amiloride were in the mid\u2010range. Tiapride (IC<jats:sub>50<\/jats:sub> = 256\u2009\u00b5 <jats:sc>m<\/jats:sc>) and K\u201027 (IC<jats:sub>50<\/jats:sub> = 414\u2009\u00b5 <jats:sc>m<\/jats:sc>) only weakly inhibited RBC AChE activity. Best <jats:italic>in vivo<\/jats:italic> protection from DFP\u2010induced mortality was achieved when physostigmine (RR = 0.02) or tacrine (RR = 0.05) was given before DFP exposure, which was significantly superior to the pretreatment with all other tested compounds, except K\u201027 (RR = 0.18). The mortality\u2010reducing effect of pyridostigmine, ranitidine and 7\u2010methoxytacrine was inferior, but still significant. Tiapride, methylene blue, metoclopramide and amiloride did not significantly improve DFP\u2010induced mortality. K\u201027 may be a more efficacious alternative to pyridostigmine, when passage into the brain precludes administration of physostigmine or tacrine. Copyright \u00a9 2010 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1589","type":"journal-article","created":{"date-parts":[[2010,10,27]],"date-time":"2010-10-27T02:35:23Z","timestamp":1288146923000},"page":"515-523","source":"Crossref","is-referenced-by-count":28,"title":["Pretreatment for acute exposure to diisopropylfluorophosphate: <i>in vivo<\/i> efficacy of various acetylcholinesterase inhibitors"],"prefix":"10.1002","volume":"31","author":[{"given":"Dietrich E.","family":"Lorke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Y.","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed M.","family":"Nurulain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Shafiullah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamil","family":"Ku\u010da","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg A.","family":"Petroianu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,10,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.2007.701"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2423(04)38006-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-4257(99)80008-4"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-200102000-00003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2005.04298.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.1996.9999"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.626929"},{"key":"e_1_2_7_9_1","first-page":"189","article-title":"Regression models and life tables","volume":"34","author":"Cox DR","year":"1972","journal-title":"J. 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