{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:23:22Z","timestamp":1789151002969,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2001,12,6]],"date-time":"2001-12-06T00:00:00Z","timestamp":1007596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to evaluate the effects of a novel antimuscarinic agent, Lu 25\u2010109, a partial M<jats:sub>1<\/jats:sub> receptor agonist, and M<jats:sub>2<\/jats:sub>\/M<jats:sub>3<\/jats:sub> receptor antagonist in human and pig detrusor to establish its affinity for muscarinic receptors in human detrusor and parotid gland and to compare the results with those obtained with oxybutynin. Effects on the detrusor were determined as regards the ability to inhibit carbachol\u2010induced contractions and contractions induced by electrical field stimulation (EFS). Radioligand binding studies were performed to assess the ability to displace quinuclidinyl benzilate (<jats:sup>3<\/jats:sup>H\u2010QNB) from muscarinic receptors in the detrusor and parotid gland. Lu 25\u2010109 produced a concentration\u2010dependent rightward shift of the concentration\u2010response curves for carbachol in both human and pig detrusor, the pK<jats:sub>b<\/jats:sub> values being 6.2\u2009\u00b1\u20090.1 (n\u2009=\u20096) and 5.8\u2009\u00b1\u20090.3 (n\u2009=\u20096). Corresponding values for oxybutynin were 7.9\u2009\u00b1\u20090.1 (n\u2009=\u20097) and 7.8\u2009\u00b1\u20090.1 (n\u2009=\u20096). Contractions induced by EFS in human detrusor were almost completely inhibited by 100 \u03bcmol\/L Lu 25\u2010109 (84\u2009\u00b1\u20094%; n\u2009=\u20094). In contrast, EFS\u2010induced contractions in pig detrusor were less sensitive to Lu 25\u2010109, resulting in a final inhibition of 32\u2009\u00b1\u20096% (n\u2009=\u20099) with the highest concentration used (100 \u03bcmol\/L). This difference in effect between human and pig detrusor was not observed with oxybutynin. Radioligand binding experiments demonstrated a small difference in affinity for Lu 25\u2010109 in the parotid gland compared with the bladder, the pK<jats:sub>i<\/jats:sub> values being 6.2\u2009\u00b1\u20090.1 versus 6.5\u2009\u00b1\u20090.1 (n\u2009=\u20094). Corresponding values for oxybutynin were 8.5\u2009\u00b1\u20090.1 versus 8.2\u2009\u00b1\u20090.1 (n\u2009=\u20094). The results show that Lu 25\u2010109 competitively and effectively antagonizes carbachol\u2010induced contractions and contractions induced by EFS in human detrusor muscle. Even if Lu 25\u2010109 were less potent than oxybutynin, it has an effect profile that makes it of interest to test its ability to counteract bladder overactivity in humans. Neurourol. Urodynam. 21:92\u201398, 2002. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/nau.2124","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T22:16:03Z","timestamp":1030313763000},"page":"92-98","source":"Crossref","is-referenced-by-count":5,"title":["Actions of the new antimuscarinic compound lu 25\u2010109 on isolated human and pig detrusor"],"prefix":"10.1002","volume":"21","author":[{"given":"K.","family":"Waldeck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Larsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Sandberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.\u2010E.","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-8673.1985.tb00120.x"},{"key":"e_1_2_1_3_1","first-page":"458","article-title":"Classification of the presynaptic muscarinic receptor subtype that regulates 3H\u2010acetylcholine secretion in the guinea pig urinary bladder in vitro","volume":"274","author":"Alberts P","year":"1995","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_1_4_1","first-page":"253","article-title":"Pharmacology of lower urinary tract smooth muscles and penile erectile tissues","volume":"45","author":"Andersson K\u2010E","year":"1993","journal-title":"Pharmacol Rev"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1464-410x.1999.00397.x"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1988.tb00974.x"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)38030-8"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(87)90110-X"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1998.274.2.R517"},{"key":"e_1_2_1_10_1","first-page":"279","article-title":"International Union of Pharmacology. 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