{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:28:46Z","timestamp":1760297326662},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3500,"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":[[1999,7]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Seven esters of \u03b1\u2010truxillic acid have been synthesized: bis\u20103\u2010piperidylpropyl ester and its quaternary bis\u2010N\u2010ethyl derivative, bis\u2010N\u2010diethylaminopropyl ester and its quaternary bis\u2010N\u2010methyl derivative, and bis\u20104\u2010piperidylbutyl ester and its quaternary bis\u2010N\u2010methyl and bis\u2010N\u2010ethyl derivatives.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All esters inhibited the specific binding of muscarinic receptor antagonist <jats:italic>[methyl\u2010<jats:sup>3<\/jats:sup>H]<\/jats:italic>\u2010N\u2010methylscopolamine ([<jats:sup>3<\/jats:sup>H]\u2010NMS) to muscarinic receptors in membranes of CHO cell lines stably expressing the human gene for the M<jats:sub>1<\/jats:sub>, M<jats:sub>2<\/jats:sub>, M<jats:sub>3<\/jats:sub> or M<jats:sub>4<\/jats:sub> subtype of muscarinic receptors. All esters displayed the highest potency at the M<jats:sub>2<\/jats:sub> and the lowest potency at the M<jats:sub>3<\/jats:sub> receptor subtype.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In experiments performed on the M<jats:sub>2<\/jats:sub> muscarinic receptor subtype, the affinity between the receptors and the esters was greatly increased when the concentration of ions was diminished. The highest affinities were found for the tertiary bis\u20103\u2010piperidylpropyl and bis\u20104\u2010piperidylbutyl aminoesters (equilibrium dissociation constants of 52 and 179\u2003pM, respectively, in the low ionic strength medium).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All investigated esters slowed down the dissociation of [<jats:sup>3<\/jats:sup>H]\u2010NMS from the M<jats:sub>2<\/jats:sub> muscarinic receptor subtype. [<jats:sup>3<\/jats:sup>H]\u2010NMS dissociation from the M<jats:sub>1<\/jats:sub>, M<jats:sub>3<\/jats:sub> and M<jats:sub>4<\/jats:sub> muscarinic receptor subtypes was investigated in experiments with the bis\u20104\u2010piperidylbutyl aminoester and also found to be decelerated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>It is concluded that the esters of \u03b1\u2010truxillic acid act as M<jats:sub>2<\/jats:sub>\u2010selective allosteric modulators of muscarinic receptors and that, by their potency, the tertiary bis\u20103\u2010piperidylpropyl and bis\u20104\u2010piperidylbutyl aminoesters surpass the other known allosteric modulators of these receptors.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1999) <jats:bold>127<\/jats:bold>, 1240\u20131246; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0702646\">10.1038\/sj.bjp.0702646<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0702646","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:16:44Z","timestamp":1106943404000},"page":"1240-1246","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Subtype\u2010selective inhibition of <i>[methyl\u2010<sup>3<\/sup>H]<\/i>\u2010N\u2010methylscopolamine binding to muscarinic receptors by \u03b1\u2010truxillic acid esters"],"prefix":"10.1111","volume":"127","author":[{"given":"Michaela","family":"Lys\u00edkov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kv\u011bta","family":"Fuksov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1\u0161","family":"Elbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Jakub\u00edk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislav","family":"Tu\u010dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"3","article-title":"Investigations of the series of cyclobutanedicarbonyl acids. 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