{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T05:23:11Z","timestamp":1736227391519,"version":"3.32.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2005,12,16]],"date-time":"2005-12-16T00:00:00Z","timestamp":1134691200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Naunyn Schmied Arch Pharmacol"],"published-print":{"date-parts":[[2006,1]]},"DOI":"10.1007\/s00210-005-0023-4","type":"journal-article","created":{"date-parts":[[2005,12,16]],"date-time":"2005-12-16T11:45:36Z","timestamp":1134733536000},"page":"267-276","source":"Crossref","is-referenced-by-count":12,"title":["Allosteric site in M2 acetylcholine receptors: evidence for a major conformational change upon binding of an orthosteric agonist instead of an antagonist"],"prefix":"10.1007","volume":"372","author":[{"given":"Maren","family":"Gro\u00dfm\u00fcller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Antony","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Tr\u00e4nkle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Holzgrabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus","family":"Mohr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2005,12,16]]},"reference":[{"issue":"3(3\u20134)","key":"23_CR1","first-page":"48","volume":"16","author":"O Arunlakshana","year":"1950","unstructured":"Arunlakshana O, Schild (1950) The air-perfused bronchial tree. J Physiol. 16,3(3\u20134):48p","journal-title":"J Physiol"},{"key":"23_CR2","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1021\/jm00036a008","volume":"37","author":"HM Botero Cid","year":"1994","unstructured":"Botero Cid HM, Holzgrabe U, Kostenis E, Mohr K, Tr\u00e4nkle C (1994) Search for the pharmacophore of bispyridinium-type allosteric modulators of muscarinic receptors. J Med Chem 37:1439\u20131445","journal-title":"J Med Chem"},{"key":"23_CR3","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/PL00005180","volume":"357","author":"U Burgmer","year":"1998","unstructured":"Burgmer U, Schulz U, Tr\u00e4nkle C, Mohr K (1998) Interaction of Mg2+ with the allosteric site of muscarinic M2 receptors. Naunyn Schmiedebergs Arch Pharmacol 357:363\u2013370","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"23_CR4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1124\/mol.61.1.160","volume":"61","author":"S Buller","year":"2002","unstructured":"Buller S, Zlotos DP, Mohr K, Ellis J (2002) Allosteric site on muscarinic acetylcholine receptors: a single amino acid in TM7 is critical to the subtype selectivities of caracurine V derivatives and alkane-bisammonium ligands. Mol Pharmacol 61:160\u2013168","journal-title":"Mol Pharmacol"},{"key":"23_CR5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.2174\/1389557054023251","volume":"5","author":"NJ Birdsall","year":"2005","unstructured":"Birdsall NJ, Lazareno S (2005) Allosterism at muscarinic receptors: ligands and mechanisms. Mini Rev Med Chem 5:523\u2013543","journal-title":"Mini Rev Med Chem"},{"key":"23_CR6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1124\/pr.54.2.323","volume":"54","author":"A Christopoulos","year":"2002","unstructured":"Christopoulos A, Kenakin T (2002) G protein-coupled receptor allosterism and complexing. Pharmacol Rev 54:323\u2013374","journal-title":"Pharmacol Rev"},{"key":"23_CR7","first-page":"187","volume":"35","author":"FJ Ehlert","year":"1988","unstructured":"Ehlert FJ (1988) Estimation of the affinities of allosteric ligands using radioligand binding and pharmacological null methods. Mol Pharmacol 35:187\u2013194","journal-title":"Mol Pharmacol"},{"key":"23_CR8","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/(SICI)1098-2299(199702)40:2<193::AID-DDR9>3.0.CO;2-G","volume":"40","author":"J Ellis","year":"1997","unstructured":"Ellis J (1997) Allosteric binding sites on muscarinic receptors. Drug Dev Res 40:193\u2013204","journal-title":"Drug Dev Res"},{"key":"23_CR9","first-page":"638","volume":"42","author":"J Ellis","year":"1992","unstructured":"Ellis J, Seidenberg M (1992) Two allosteric modulators interact at a common site on cardiac muscarinic receptors. Mol Pharmacol 42:638\u2013641","journal-title":"Mol Pharmacol"},{"key":"23_CR10","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1124\/mol.58.6.1451","volume":"58","author":"J Ellis","year":"2000","unstructured":"Ellis J, Seidenberg M (2000) Interactions of alcuronium, TMB-8, and other allosteric ligands with muscarinic acetylcholine receptors: studies with chimeric receptors. Mol Pharmacol 58:1451\u20131460","journal-title":"Mol Pharmacol"},{"key":"23_CR11","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1023\/A:1022858414900","volume":"28","author":"R Gilsbach","year":"2003","unstructured":"Gilsbach R, Gro\u00dfm\u00fcller M, Alpt\u00fcz\u00fcn V, Erciyas E, Tr\u00e4nkle C, Holzgrabe U, Mohr K (2003) Cooperative interactions at M2 muscarinic acetylcholine interactions: Structure\/activity-relationships in stepwise shortened bispyridinium- and bis(ammonio)alkane-type allosteric modulators. Neurochem Res 28:667\u2013673","journal-title":"Neurochem Res"},{"key":"23_CR12","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/S0006-2952(96)00598-9","volume":"52","author":"A Gnagey","year":"1996","unstructured":"Gnagey A, Ellis J (1996) Allosteric regulation of the binding of [3H]acetylcholine to m2 muscarinic receptors. Biochem Pharmacol 52:1767\u20131775","journal-title":"Biochem Pharmacol"},{"key":"23_CR13","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1124\/mol.56.6.1245","volume":"56","author":"AL Gnagey","year":"1999","unstructured":"Gnagey AL, Seidenberg M, Ellis J (1999) Site-directed mutagenesis reveals two epitopes involved in the subtype selectivity of the allosteric interactions of gallamine at muscarinic acetylcholine receptors. Mol Pharmacol 56:1245\u20131253","journal-title":"Mol Pharmacol"},{"key":"23_CR14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0014-2999(99)00439-2","volume":"380","author":"F Heitz","year":"1999","unstructured":"Heitz F, Holzwarth JA, Gies JP, Pruss RM, Trumpp-Kallmeyer S, Hibert MF, Guenet C (1999) Site-directed mutagenesis of the putative human muscarinic M2 receptor binding site. Eur J Pharmacol 380:183\u2013195","journal-title":"Eur J Pharmacol"},{"key":"23_CR15","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/S1359-6446(97)01161-6","volume":"3","author":"U Holzgrabe","year":"1998","unstructured":"Holzgrabe U, Mohr K (1998) Allosteric modulators of ligand binding to muscarinic acetylcholine receptors. Drug Discovery Today 3:214\u2013222","journal-title":"Drug Discovery Today"},{"key":"23_CR16","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1124\/mol.105.014043","volume":"68","author":"XP Huang","year":"2005","unstructured":"Huang XP, Prilla S, Mohr K, Ellis J (2005) Critical amino acid residues of the common allosteric site on the M2 muscarinic acetylcholine receptor: more similarities than differences between the structurally divergent agents gallamine and bis(ammonio)alkane-type W84. Mol Pharmacol 68:769\u2013778","journal-title":"Mol Pharmacol"},{"issue":"Pt 1","key":"23_CR17","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1042\/bst0310029","volume":"31","author":"EC Hulme","year":"2003","unstructured":"Hulme EC, Lu ZL, Saldanha JW, Bee MS (2003) Structure and activation of muscarinic acetylcholine receptors. Biochem Soc Trans. 31(Pt 1):29\u201334","journal-title":"Biochem Soc Trans"},{"key":"23_CR18","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1124\/mol.52.1.172","volume":"52","author":"J Jakub\u00edk","year":"1997","unstructured":"Jakub\u00edk J, Ba\u010d\u00e1kov\u00e1 L, El-Fakahany EE, Tu\u010dek S (1997) Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors. Mol Pharmacol 52:172\u2013179","journal-title":"Mol Pharmacol"},{"key":"23_CR19","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1023\/A:1023880611709","volume":"16","author":"K J\u00f6hren","year":"2002","unstructured":"J\u00f6hren K, H\u00f6ltje H-D (2002) A model of the human M2 muscarinic acetylcholine receptor. J Comput Aided Mol Des 16:795\u2013801","journal-title":"J Comput Aided Mol Des"},{"key":"23_CR20","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/0223-5234(94)90194-5","volume":"29","author":"E Kostenis","year":"1994","unstructured":"Kostenis E, Holzgrabe U, Mohr K (1994) Allosteric effect on muscarinic M2-receptors of derivatives of the alkane-bis-ammonium compound W84. Comparison with bispyridinium-type allosteric modulators. Eur J Med Chem 29:947\u2013953","journal-title":"Eur J Med Chem"},{"key":"23_CR21","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0165-6147(97)88188-6","volume":"17","author":"E Kostenis","year":"1996","unstructured":"Kostenis E, Mohr K (1996) Composite action of allosteric modulators on ligand binding. Trends Pharmacol Sci 17:443\u2013444","journal-title":"Trends Pharmacol Sci"},{"key":"23_CR22","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S0026-895X(24)12303-6","volume":"60","author":"A Krej\u010di","year":"2001","unstructured":"Krej\u010di A, Tu\u010dek S (2001) Changes of cooperativity between N-methylscopolamine and allosteric modulators alcuronium and gallamine induced by mutations of external loops of muscarinic M(3) receptors. Mol Pharmacol 60:761\u2013767","journal-title":"Mol Pharmacol"},{"issue":"Suppl 1","key":"23_CR23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.33549\/physiolres.930000.53.S131","volume":"53","author":"A Krej\u010d\u00ed","year":"2004","unstructured":"Krej\u010d\u00ed A, Michal P, Jakub\u00edk J, \u0158\u00ed\u010dn\u00fd J, Dole\u017eal V (2004) Regulation of signal transduction at M2 muscarinic receptor. Physiol Res 53 Suppl 1:131\u2013140","journal-title":"Physiol Res"},{"key":"23_CR24","first-page":"362","volume":"48","author":"S Lazareno","year":"1995","unstructured":"Lazareno S, Birdsall NJM (1995) Detection, quantification and verification of allosteric interactions of agents with labeled and unlabeled ligands at G-protein-coupled receptors: Interaction of strychnine and acetylcholine at muscarinic receptors. Mol Pharmacol 48:362\u2013378","journal-title":"Mol Pharmacol"},{"key":"23_CR25","first-page":"983","volume":"45","author":"RA Leppik","year":"1994","unstructured":"Leppik RA, Miller RC, Eck M, Paquet JL (1994) Role of acidic amino acids in the allosteric modulation by gallamine of antagonist binding at the m2 muscarinic acetylcholine receptor. Mol Pharmacol 45:983\u2013990","journal-title":"Mol Pharmacol"},{"key":"23_CR26","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S0165-6147(00)01973-8","volume":"23","author":"ZL Lu","year":"2002","unstructured":"Lu ZL, Saldanha JW, Hulme EC (2002) Seven-transmembrane receptors: crystals clarify. Trends Pharmacol Sci 23:140\u2013146","journal-title":"Trends Pharmacol Sci"},{"key":"23_CR27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0014-2999(96)00240-3","volume":"305","author":"A Maa\u00df","year":"1996","unstructured":"Maa\u00df A, Mohr K (1996) Opposite effects of alcuronium on agonist and on antagonist binding to muscarinic receptors. Eur J Pharmacol 305:231\u2013234","journal-title":"Eur J Pharmacol"},{"key":"23_CR28","first-page":"55","volume":"Suppl","author":"C Melchiorre","year":"1989","unstructured":"Melchiorre C, Minarini A, Angeli P, Giardina D, Gulini U, Quaglia W (1989) Polymethylene tetraamines as muscarinic receptor probes. Trends Pharmacol Sci (Suppl) 55\u201359","journal-title":"Trends Pharmacol Sci"},{"key":"23_CR29","first-page":"229","volume":"9","author":"K Mohr","year":"2003","unstructured":"Mohr K, Tr\u00e4nkle C, Holzgrabe U (2003) Structure\/activity relationships of M2 muscarinic allosteric modulators. Receptors Channels 9:229\u2013240","journal-title":"Receptors Channels"},{"key":"23_CR30","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1021\/jm031095t","volume":"47","author":"M Mohr","year":"2004","unstructured":"Mohr M, Heller E, Ataie A, Mohr K, Holzgrabe U (2004) Development of a new type of allosteric modulator of muscarinic receptors: hybrids of the antagonist AF-DX 384 and the hexamethonio derivative W84 J Med Chem 47:3324\u20133327","journal-title":"J Med Chem"},{"key":"23_CR31","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1021\/jm021017q","volume":"46","author":"M Muth","year":"2003","unstructured":"Muth M, Bender W, Scharfenstein O, Holzgrabe U, Balatkov\u00e1 E, Tr\u00e4nkle C, Mohr K (2003) Systematic development of high affinity bis(ammonio)alkane-type allosteric enhancers of muscarinic ligand binding. J Med Chem 46:1031\u20131040","journal-title":"J Med Chem"},{"key":"23_CR32","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1021\/jm049616f","volume":"48","author":"M Muth","year":"2005","unstructured":"Muth M, Sennwitz M, Mohr K, Holzgrabe U (2005) Muscarinic allosteric enhancers of ligand binding: pivotal pharmacophoric elements in hexamethonio-type agents. J Med Chem 48:2212\u20132217","journal-title":"J Med Chem"},{"key":"23_CR33","first-page":"211","volume":"39","author":"LT Potter","year":"1991","unstructured":"Potter LT, Ballesteros LA, Bichajian LH, Ferrendelli CA, Fisher A, Hanchett HE, Zhang R (1991) Evidence of paired M2 muscarinic receptors. Mol Pharmacol 39:211\u2013221","journal-title":"Mol Pharmacol"},{"key":"23_CR34","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s002100000316","volume":"362","author":"A Schr\u00f6ter","year":"2000","unstructured":"Schr\u00f6ter A, Tr\u00e4nkle C, Mohr K (2000) Modes of allosteric interactions with free and [3H]N-methylscopolamine-occupied muscarinic M2 receptors as deduced from buffer-dependent potency shifts. Naunyn Schmiedebergs Arch Pharmacol 362:512\u2013519","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"23_CR35","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/S1359-6446(04)03220-9","volume":"9","author":"W Soudijn","year":"2004","unstructured":"Soudijn W, van Wijngaarden I, IJzerman AP (2004) Allosteric modulation of G protein-coupled receptors: perspectives and recent developments. Drug Discov Today 9:752\u2013758","journal-title":"Drug Discov Today"},{"key":"23_CR36","first-page":"551","volume":"23","author":"JM Stockton","year":"1983","unstructured":"Stockton JM, Birdsall NJM, Burgen ASV, Hulme EC (1983) Modification of the binding properties of muscarinic receptors by gallamine. Mol Pharmacol 23:551\u2013557","journal-title":"Mol Pharmacol"},{"issue":"4","key":"23_CR37","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1124\/mol.51.4.674","volume":"51","author":"C Tr\u00e4nkle","year":"1997","unstructured":"Tr\u00e4nkle C, Mohr K (1997) Divergent modes of action among cationic allosteric modulators of muscarinic M2 receptors. Mol Pharmacol 51(4):674\u2013682","journal-title":"Mol Pharmacol"},{"key":"23_CR38","first-page":"926","volume":"279","author":"C Tr\u00e4nkle","year":"1996","unstructured":"Tr\u00e4nkle C, Kostenis E, Burgmer U, Mohr K (1996) Search for lead structures to develop new allosteric modulators of muscarinic receptors. J Pharmacol Exp Ther 279:926\u2013933","journal-title":"J Pharmacol Exp Ther"},{"key":"23_CR39","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1124\/mol.53.2.304","volume":"53","author":"C Tr\u00e4nkle","year":"1998","unstructured":"Tr\u00e4nkle C, Andresen I, Lambrecht G, Mohr K (1998) M2 receptor binding of the selective antagonist AF-DX 384: possible involvement of the common allosteric site. Mol Pharmacol 53:304\u2013312","journal-title":"Mol Pharmacol"},{"key":"23_CR40","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1124\/mol.105.017707","volume":"68","author":"C Tr\u00e4nkle","year":"2005","unstructured":"Tr\u00e4nkle C, Dittmann A, Schulz U, Weyand O, Buller S, J\u00f6hren K, Heller E, Birdsall NJM, Holzgrabe U, Ellis J, H\u00f6ltje HDH, Mohr K (2005) Atypical muscarinic allosteric modulation: cooperativity between modulators and their atypical binding topology in muscarinic M2 and M2\/M5 chimeric receptors. Mol Pharmacol 68:1597\u20131610","journal-title":"Mol Pharmacol"},{"key":"23_CR41","first-page":"674","volume":"38","author":"S Tu\u010dek","year":"1990","unstructured":"Tu\u010dek S, Mus\u00edlkov\u00e1 J, Nedoma J, Pro\u0161ka J, Shelkovnikov S, Vorl\u00ed\u010dek J (1990) Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors. Mol Pharmacol 38:674\u2013680","journal-title":"Mol Pharmacol"},{"key":"23_CR42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1124\/mol.64.1.21","volume":"64","author":"U Voigtl\u00e4nder","year":"2003","unstructured":"Voigtl\u00e4nder U, J\u00f6hren K, Mohr M, Raasch A, Tr\u00e4nkle C, Buller S, Ellis J, H\u00f6ltje HD, Mohr K (2003) Allosteric site on muscarinic acetylcholine receptors: Identification of two amino acids in the muscarinic M2 receptor that account entirely for the M2\/M5 subtype selectivities of some structurally diverse allosteric ligands in N-methylscoplamine occupied receptors. Mol Pharmacol 64:21\u201331","journal-title":"Mol Pharmacol"},{"key":"23_CR43","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1124\/mol.105.019141","volume":"68","author":"J Wess","year":"2005","unstructured":"Wess J (2005) Allosteric binding sites on muscarinic acetylcholine receptors (Relates to article by Tr\u00e4nkle et al.) Mol Pharmacol 68:1506\u20131509","journal-title":"Mol Pharmacol"},{"key":"23_CR44","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1124\/jpet.301.2.720","volume":"301","author":"K Zahn","year":"2002","unstructured":"Zahn K, Eckstein N, Tr\u00e4nkle C, Sade\u00e9 W, Mohr, K. (2002). Allosteric modulation of muscarinic receptor signaling: Alcuronium-induced conversion of pilocarpine from an agonist into an antagonist. J Pharmacol Exp Ther 301:720\u2013728","journal-title":"J Pharmacol Exp Ther"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-005-0023-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00210-005-0023-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-005-0023-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T15:16:38Z","timestamp":1736176598000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00210-005-0023-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,16]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,1]]}},"alternative-id":["23"],"URL":"https:\/\/doi.org\/10.1007\/s00210-005-0023-4","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"type":"print","value":"0028-1298"},{"type":"electronic","value":"1432-1912"}],"subject":[],"published":{"date-parts":[[2005,12,16]]}}}