{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T11:06:58Z","timestamp":1777460818418,"version":"3.51.4"},"reference-count":52,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["HO1368\/12-1"],"award-info":[{"award-number":["HO1368\/12-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["KO1582\/3-1"],"award-info":[{"award-number":["KO1582\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["MO821\/2-1"],"award-info":[{"award-number":["MO821\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2014,8]]},"DOI":"10.1016\/j.bcp.2014.05.012","type":"journal-article","created":{"date-parts":[[2014,5,23]],"date-time":"2014-05-23T14:02:31Z","timestamp":1400853751000},"page":"307-319","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["New insight into active muscarinic receptors with the novel radioagonist [3H]iperoxo"],"prefix":"10.1016","volume":"90","author":[{"given":"Ramona","family":"Schrage","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Holze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Kl\u00f6ckner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aileen","family":"Balkow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne S.","family":"Klause","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna-Lena","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"De Amici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evi","family":"Kostenis","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":"78","reference":[{"key":"10.1016\/j.bcp.2014.05.012_bib0005","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/nature08144","article-title":"The structure and function of G-protein-coupled receptors","volume":"459","author":"Rosenbaum","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0010","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/nrd2518","article-title":"Structural diversity of G protein-coupled receptors and significance for drug discovery","volume":"7","author":"Lagerstr\u00f6m","year":"2008","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bcp.2014.05.012_bib0015","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nrm2299","article-title":"Heterotrimeric G protein activation by G-protein-coupled receptors","volume":"9","author":"Oldham","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0020","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1146\/annurev.pharmtox.44.101802.121622","article-title":"Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications","volume":"44","author":"Wess","year":"2004","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0025","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1124\/mol.63.6.1256","article-title":"The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints","volume":"63","author":"Fredriksson","year":"2003","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0030","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1038\/nrd2379","article-title":"Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development","volume":"6","author":"Wess","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bcp.2014.05.012_bib0035","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1124\/mol.113.087551","article-title":"Muscarinic receptors as model targets and antitargets for structure-based ligand discovery","volume":"84","author":"Kruse","year":"2013","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0040","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tips.2008.12.002","article-title":"Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders","volume":"30","author":"Conn","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.bcp.2014.05.012_bib0045","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/S0968-0896(99)00107-8","article-title":"Synthesis and functional characterization of novel derivatives related to oxotremorine and oxotremorine-M","volume":"7","author":"Dallanoce","year":"1999","journal-title":"Bioorg Med Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0050","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1016\/j.tetlet.2010.04.130","article-title":"Convergent, short synthesis of the muscarinic superagonist iperoxo","volume":"51","author":"Kloeckner","year":"2010","journal-title":"Tetrahedron Lett"},{"key":"10.1016\/j.bcp.2014.05.012_bib0055","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/bph.12003","article-title":"Agonists with supraphysiological efficacy at the muscarinic M 2 ACh receptor","volume":"169","author":"Schrage","year":"2013","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0060","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature10753","article-title":"Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist","volume":"482","author":"Haga","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0065","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature12735","article-title":"Activation and allosteric modulation of a muscarinic acetylcholine receptor","volume":"504","author":"Kruse","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0070","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1124\/mol.113.085670","article-title":"Exploration of the orthosteric\/allosteric interface in human M1 muscarinic receptors by bitopic fluorescent ligands","volume":"84","author":"Daval","year":"2013","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0075","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00210-005-0023-4","article-title":"Allosteric site in M2 acetylcholine receptors: evidence for a major conformational change upon binding of an orthosteric agonist instead of an antagonist","volume":"372","author":"Grossm\u00fcller","year":"2006","journal-title":"Naunyn-Schmied Arch Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0080","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/S0006-2952(96)00598-9","article-title":"Allosteric regulation of the binding of [3H]acetylcholine to m2 muscarinic receptors","volume":"52","author":"Gnagey","year":"1996","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0085","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/nature10867","article-title":"Structure and dynamics of the M3 muscarinic acetylcholine receptor","volume":"482","author":"Kruse","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0090","doi-asserted-by":"crossref","first-page":"7108","DOI":"10.1016\/S0021-9258(20)79672-9","article-title":"A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor","volume":"255","author":"De Lean","year":"1980","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0095","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1111\/j.1476-5381.2011.01749.x","article-title":"Biased signalling and allosteric machines: new vistas and challenges for drug discovery","volume":"165","author":"Kenakin","year":"2012","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0100","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0014-2999(69)90181-2","article-title":"Inhibition of the actions of carbachol and DFP on guinea pig isolated atria by alkane-bis-ammonium compounds","volume":"6","author":"L\u00fcllmann","year":"1969","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0105","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1111\/j.1476-5381.1976.tb07708.x","article-title":"The inhibitory effect of gallamine on muscarinic receptors","volume":"58","author":"Clark","year":"1976","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0110","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0026-895X(25)14327-7","article-title":"Modification of the binding properties of muscarinic receptors by gallamine","volume":"23","author":"Stockton","year":"1983","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0115","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1124\/mol.106.023481","article-title":"Allosteric interactions with muscarinic acetylcholine receptors: complex role of the conserved tryptophan M2422Trp in a critical cluster of amino acids for baseline affinity, subtype selectivity, and cooperativity","volume":"70","author":"Prilla","year":"2006","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0120","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature12595","article-title":"Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs","volume":"503","author":"Dror","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0125","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/ncomms2028","article-title":"The allosteric vestibule of a seven transmembrane helical receptor controls G-protein coupling","volume":"3","author":"Bock","year":"2012","journal-title":"Nat Commun"},{"key":"10.1016\/j.bcp.2014.05.012_bib0130","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0135","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1096\/fj.08-114751","article-title":"Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity","volume":"23","author":"Antony","year":"2009","journal-title":"FASEB J"},{"key":"10.1016\/j.bcp.2014.05.012_bib0140","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1016\/0006-2952(73)90196-2","article-title":"Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction","volume":"22","author":"Cheng","year":"1973","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0145","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0165-6147(89)90266-6","article-title":"Calculating receptor number from binding experiments using same compound as radioligand and competitor","volume":"10","author":"De Blasi","year":"1989","journal-title":"Trends Pharmacol Sci"},{"key":"10.1016\/j.bcp.2014.05.012_bib0150","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0006-2952(99)00087-8","article-title":"Qualitative and quantitative assessment of relative agonist efficacy","volume":"58","author":"Christopoulos","year":"1999","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0155","doi-asserted-by":"crossref","first-page":"29312","DOI":"10.1074\/jbc.M803801200","article-title":"A novel mechanism of G protein-coupled receptor functional selectivity: muscarinic partial agonist McN-A-343 as a bitopic orthosteric\/allosteric ligand","volume":"283","author":"Valant","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0160","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0026-895X(25)11048-1","article-title":"Partial agonist effects on the interaction between the atrial muscarinic receptor and the inhibitory guanine nucleotide-binding protein in a reconstituted system","volume":"37","author":"Tota","year":"1990","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0165","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/sj.bjp.0706090","article-title":"An investigation of whether agonist-selective receptor conformations occur with respect to M2 and M4 muscarinic acetylcholine receptor signalling via Gi\/o and Gs proteins","volume":"144","author":"Mistry","year":"2005","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0170","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1124\/jpet.107.120857","article-title":"Estimation of agonist activity at G protein-coupled receptors: analysis of M2 muscarinic receptor signaling through Gi\/o,Gs, and G15","volume":"321","author":"Griffin","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.bcp.2014.05.012_bib0175","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1124\/jpet.106.114314","article-title":"Muscarinic M2 receptors directly activate Gq\/11 and Gs G-proteins","volume":"320","author":"Michal","year":"2007","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.bcp.2014.05.012_bib0180","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/sj.bjp.0707672","article-title":"Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors","volume":"153","author":"Strange","year":"2008","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0185","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0065-3233(07)74004-4","article-title":"Activation of G protein-coupled receptors","volume":"74","author":"Deupi","year":"2007","journal-title":"Adv Protein Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0190","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/nature07330","article-title":"Crystal structure of opsin in its G-protein-interacting conformation","volume":"455","author":"Scheerer","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0195","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature10361","article-title":"Crystal structure of the \u03b22 adrenergic receptor\u2013Gs protein complex","volume":"477","author":"Rasmussen","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0200","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0026-895X(25)13545-1","article-title":"The binding of agonists to brain muscarinic receptors","volume":"14","author":"Birdsall","year":"1978","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0205","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/S0026-895X(25)13743-7","article-title":"Muscarinic receptor heterogeneity in rat central nervous system. II. Brain receptors labeled by [3H]oxotremorine-M correspond to heterogeneous M2 receptors with very high affinity for agonists","volume":"32","author":"Gillard","year":"1987","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0210","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1177\/1087057110369702","article-title":"Screening a plant extract library for inhibitors of cholecystokinin receptor CCK1 pathways","volume":"15","author":"Nesterov","year":"2010","journal-title":"J Biomol Screen"},{"key":"10.1016\/j.bcp.2014.05.012_bib0215","doi-asserted-by":"crossref","first-page":"ra93","DOI":"10.1126\/scisignal.2004350","article-title":"Decoding signaling and function of the orphan G protein-coupled receptor GPR17 with a small-molecule agonist","volume":"6","author":"Hennen","year":"2013","journal-title":"Sci Signal"},{"key":"10.1016\/j.bcp.2014.05.012_bib0220","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1016\/S0024-3205(01)01047-5","article-title":"Multiple allosteric sites on muscarinic receptors","volume":"68","author":"Birdsall","year":"2001","journal-title":"Life Sci"},{"key":"10.1016\/j.bcp.2014.05.012_bib0225","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.bcp.2012.03.008","article-title":"The role of the second and third extracellular loops of the adenosine A1 receptor in activation and allosteric modulation","volume":"84","author":"Peeters","year":"2012","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0230","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.bcp.2013.03.005","article-title":"The second extracellular loop of GPCRs determines subtype-selectivity and controls efficacy as evidenced by loop exchange study at A2 adenosine receptors","volume":"85","author":"Seibt","year":"2013","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0235","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.bcp.2010.06.041","article-title":"Characterization of [3H]LUF5834: A novel non-ribose high-affinity agonist radioligand for the adenosine A1 receptor","volume":"80","author":"Lane","year":"2010","journal-title":"Biochem Pharmacol"},{"key":"10.1016\/j.bcp.2014.05.012_bib0240","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1096\/fj.00-0438rev","article-title":"Inverse, protean, and ligand-selective agonism: matters of receptor conformation","volume":"15","author":"Kenakin","year":"2001","journal-title":"FASEB J"},{"key":"10.1016\/j.bcp.2014.05.012_bib0245","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nature12120","article-title":"Structure of active \u03b2-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide","volume":"497","author":"Shukla","year":"2013","journal-title":"Nature"},{"key":"10.1016\/j.bcp.2014.05.012_bib0250","doi-asserted-by":"crossref","first-page":"37066","DOI":"10.1074\/jbc.M112.408534","article-title":"Stimulus bias provides evidence for conformational constraints in the structure of a G protein-coupled receptor","volume":"287","author":"Gregory","year":"2012","journal-title":"J Biol Chem"},{"key":"10.1016\/j.bcp.2014.05.012_bib0255","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1124\/pr.108.000992","article-title":"Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery","volume":"62","author":"Kenakin","year":"2010","journal-title":"Pharmacol Rev"},{"key":"10.1016\/j.bcp.2014.05.012_bib0260","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nature12572","article-title":"Adrenaline-activated structure of \u03b22-adrenoceptor stabilized by an engineered nanobody","volume":"502","author":"Ring","year":"2013","journal-title":"Nature"}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295214002895?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295214002895?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T01:28:57Z","timestamp":1746235737000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295214002895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,8]]}},"alternative-id":["S0006295214002895"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2014.05.012","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2014,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"New insight into active muscarinic receptors with the novel radioagonist [3H]iperoxo","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2014.05.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}