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Choy","year":"2018","journal-title":"P T"},{"key":"ref54","article-title":"History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment","author":"SJ Tepper","year":"2018","journal-title":"Headache"},{"issue":"7","key":"ref55","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/bjp.2008.334","article-title":"CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat","volume":"155","author":"J Zeller","year":"2008","journal-title":"Br J Pharmacol"},{"issue":"3","key":"ref56","first-page":"768","article-title":"Pharmacology of SB-273779, a nonpeptide calcitonin gene-related peptide 1 receptor antagonist","volume":"296","author":"N Aiyar","year":"2001","journal-title":"J Pharmacol Exp Ther"},{"issue":"6","key":"ref57","first-page":"1379","article-title":"Adrenomedullin antagonist suppresses tumor formation in renal cell carcinoma through 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Breeze","year":"1991","journal-title":"Biochemistry"},{"issue":"28","key":"ref70","doi-asserted-by":"crossref","first-page":"8317","DOI":"10.1021\/bi0102860","article-title":"Turn structures in CGRP C-terminal analogues promote stable arrangements of key residue side chains","volume":"40","author":"KA Carpenter","year":"2001","journal-title":"Biochemistry"},{"issue":"6","key":"ref71","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/j.1399-3011.1996.tb01098.x","article-title":"Structural comparison of alanine-substituted analogues of the calcitonin gene-related peptide 8\u201337. 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affinity: a systematic approach to identify the binding site of CGRP at the human calcitonin gene-related peptide 1 receptor","volume":"41","author":"B Rist","year":"1998","journal-title":"J Med Chem"},{"issue":"6","key":"ref75","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1021\/jm061343w","article-title":"Calcitonin gene-related peptide analogues with aza and indolizidinone amino acid residues reveal conformational requirements for antagonist activity at the human calcitonin gene-related peptide 1 receptor","volume":"50","author":"D Boeglin","year":"2007","journal-title":"J Med Chem"},{"issue":"7","key":"ref76","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1111\/bph.12072","article-title":"Structure-activity relationships for alpha-calcitonin gene-related peptide","volume":"170","author":"HA Watkins","year":"2013","journal-title":"Br J Pharmacol"},{"issue":"1","key":"ref77","first-page":"123","article-title":"hCGRP8-37, a calcitonin gene-related peptide antagonist revealing calcitonin gene-related peptide receptor heterogeneity in brain and periphery","volume":"254","author":"T Dennis","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"issue":"2","key":"ref78","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1021\/jm050613s","article-title":"Identification of the key residue of calcitonin gene related peptide (CGRP) 27\u201337 to obtain antagonists with picomolar affinity at the CGRP receptor","volume":"49","author":"M Lang","year":"2006","journal-title":"J Med Chem"},{"issue":"2","key":"ref79","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/pro.2003","article-title":"Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding","volume":"21","author":"S Kusano","year":"2012","journal-title":"Protein Sci"},{"issue":"1","key":"ref80","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/bph.12118","article-title":"Identification of key residues involved in adrenomedullin binding to the AM1 receptor","volume":"169","author":"HA Watkins","year":"2013","journal-title":"Br J Pharmacol"},{"issue":"88","key":"ref81","doi-asserted-by":"crossref","first-page":"20130589","DOI":"10.1098\/rsif.2013.0589","article-title":"The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach","volume":"10","author":"MJ Woolley","year":"2013","journal-title":"J R Soc Interface"},{"issue":"7724","key":"ref82","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41586-018-0535-y","article-title":"Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor","volume":"561","author":"YL Liang","year":"2018","journal-title":"Nature"},{"issue":"16","key":"ref83","doi-asserted-by":"crossref","first-page":"8686","DOI":"10.1074\/jbc.M115.713628","article-title":"Calcitonin and Amylin Receptor Peptide Interaction Mechanisms: INSIGHTS INTO PEPTIDE-BINDING MODES AND ALLOSTERIC MODULATION OF THE CALCITONIN RECEPTOR BY RECEPTOR ACTIVITY-MODIFYING PROTEINS","volume":"291","author":"SM Lee","year":"2016","journal-title":"J Biol Chem"},{"key":"ref84","article-title":"Structure-function analyses reveal a triple beta-turn receptor-bound conformation of adrenomedullin 2\/intermedin and enable peptide antagonist design","author":"AM Roehrkasse","year":"2018","journal-title":"J Biol Chem"},{"issue":"36","key":"ref85","doi-asserted-by":"crossref","first-page":"11640","DOI":"10.1002\/anie.201805208","article-title":"Solid-Phase Thiol-Ene Lipidation of Peptides for the Synthesis of a Potent CGRP Receptor Antagonist","volume":"57","author":"ET Williams","year":"2018","journal-title":"Angew Chem Int Ed Engl"},{"issue":"10","key":"ref86","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1016\/j.bbamem.2011.06.012","article-title":"Structure and membrane orientation of IAPP in its natively amidated form at physiological pH in a membrane environment","volume":"1808","author":"RP Nanga","year":"2011","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"ref87","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/bip.21700","article-title":"Structure of micelle-bound adrenomedullin: a first step toward the analysis of its interactions with receptors and small molecules","volume":"97","author":"J Perez-Castells","year":"2012","journal-title":"Biopolymers"},{"issue":"6","key":"ref88","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1517\/13543784.2012.681044","article-title":"CGRP receptor antagonists: an expanding drug class for acute migraine?","volume":"21","author":"A Negro","year":"2012","journal-title":"Expert Opin Investig Drugs"},{"issue":"7","key":"ref89","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2165\/11534920-000000000-00000","article-title":"Calcitonin gene-related peptide (CGRP) receptor antagonists in the treatment of migraine","volume":"24","author":"PL Durham","year":"2010","journal-title":"CNS Drugs"},{"issue":"11","key":"ref90","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1056\/NEJMoa030505","article-title":"Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine","volume":"350","author":"J Olesen","year":"2004","journal-title":"N Engl J Med"},{"issue":"7","key":"ref91","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/sj.bjp.0705807","article-title":"Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat","volume":"142","author":"RJ Storer","year":"2004","journal-title":"Br J Pharmacol"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1146\/annurev-pharmtox-010814-124701","article-title":"Calcitonin gene-related peptide (CGRP): a new target for migraine","volume":"55","author":"AF Russo","year":"2015","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.neuroscience.2016.06.012","article-title":"Neurovascular contributions to migraine: Moving beyond vasodilation","volume":"338","author":"B Jacobs","year":"2016","journal-title":"Neuroscience"},{"key":"ref94","article-title":"Molecular studies of CGRP and the CGRP family of peptides in the central nervous system","author":"ER Hendrikse","year":"2018","journal-title":"Cephalalgia"},{"issue":"3","key":"ref95","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/bcp.12686","article-title":"CGRP as a neuropeptide in migraine: lessons from mice","volume":"80","author":"AF Russo","year":"2015","journal-title":"Br J Clin Pharmacol"},{"issue":"20","key":"ref96","doi-asserted-by":"crossref","first-page":"4575","DOI":"10.1111\/bph.12651","article-title":"Modelling headache and migraine and its pharmacological manipulation","volume":"171","author":"SE Erdener","year":"2014","journal-title":"Br J Pharmacol"},{"issue":"27","key":"ref97","doi-asserted-by":"crossref","first-page":"8798","DOI":"10.1523\/JNEUROSCI.1727-09.2009","article-title":"Role of calcitonin gene-related peptide in light-aversive behavior: implications for migraine","volume":"29","author":"A Recober","year":"2009","journal-title":"J Neurosci"},{"issue":"9656","key":"ref98","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1016\/S0140-6736(08)61710-9","article-title":"CGRP-receptor antagonism in migraine treatment","volume":"372","author":"L. Edvinsson","year":"2008","journal-title":"Lancet"},{"issue":"7","key":"ref99","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1038\/bjp.2008.346","article-title":"CGRP blockers in migraine therapy: where do they act?","volume":"155","author":"L. Edvinsson","year":"2008","journal-title":"Br J Pharmacol"},{"issue":"5","key":"ref100","first-page":"831","article-title":"Characterizing the PK\/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist","volume":"79","author":"CC Li","year":"2014","journal-title":"Br J Clin Pharmacol"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1129-2377-14-93","article-title":"The calcitonin gene-related peptide receptor antagonist MK-8825 decreases spinal trigeminal activity during nitroglycerin infusion","volume":"14","author":"S Feistel","year":"2013","journal-title":"J Headache Pain"},{"issue":"2","key":"ref102","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1002\/ejp.616","article-title":"CGRP receptor blockade by MK-8825 alleviates allodynia in infraorbital nerve-ligated rats","volume":"19","author":"B Michot","year":"2015","journal-title":"Eur J Pain"},{"issue":"10","key":"ref103","first-page":"12967","article-title":"Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model","volume":"8","author":"A Taniguchi","year":"2015","journal-title":"Int J Clin Exp Pathol"},{"issue":"1","key":"ref104","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13018-016-0460-4","article-title":"Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1\/EP2\/EP4 receptor pathway in synovium of knee osteoarthritis patients","volume":"11","author":"A Minatani","year":"2016","journal-title":"J Orthop Surg Res"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.2147\/JPR.S135939","article-title":"Increase and regulation of synovial calcitonin gene-related peptide expression in patients with painful knee osteoarthritis","volume":"10","author":"S Takano","year":"2017","journal-title":"J Pain Res"},{"issue":"1","key":"ref106","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1186\/s12944-018-0864-8","article-title":"Regulation of calcitonin gene-related peptide expression through the COX-2\/mPGES-1\/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis","volume":"17","author":"J Aikawa","year":"2018","journal-title":"Lipids Health Dis"},{"issue":"5","key":"ref107","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/bcp.12669","article-title":"Calcitonin gene-related peptide in the joint: contributions to pain and inflammation","volume":"80","author":"DA Walsh","year":"2015","journal-title":"Br J Clin Pharmacol"},{"issue":"10","key":"ref108","doi-asserted-by":"crossref","first-page":"e77824","DOI":"10.1371\/journal.pone.0077824","article-title":"The inhibition of subchondral bone lesions significantly reversed the weight-bearing deficit and the overexpression of CGRP in DRG neurons, GFAP and Iba-1 in the spinal dorsal horn in the monosodium iodoacetate induced model of osteoarthritis pain","volume":"8","author":"D Yu","year":"2013","journal-title":"PLoS One"},{"issue":"8","key":"ref109","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1002\/art.38656","article-title":"Peripheral calcitonin gene-related peptide receptor activation and mechanical sensitization of the joint in rat models of osteoarthritis pain","volume":"66","author":"CM Bullock","year":"2014","journal-title":"Arthritis Rheumatol"},{"issue":"9","key":"ref110","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/j.1532-2149.2014.493.x","article-title":"Involvement of adrenomedullin in spinal glial activation following chronic administration of morphine in rats","volume":"18","author":"X Zeng","year":"2014","journal-title":"Eur J Pain"},{"issue":"1","key":"ref111","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.bbr.2011.02.046","article-title":"Blockade of adrenomedullin receptors reverses morphine tolerance and its neurochemical mechanisms","volume":"221","author":"D Wang","year":"2011","journal-title":"Behav Brain Res"},{"issue":"43","key":"ref112","doi-asserted-by":"crossref","first-page":"16027","DOI":"10.1073\/pnas.0602488103","article-title":"A role for adrenomedullin as a pain-related peptide in the rat","volume":"103","author":"W Ma","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ref113","doi-asserted-by":"crossref","first-page":"4908","DOI":"10.1210\/en.2010-0121","article-title":"Lack of adrenomedullin in the central nervous system results in apparently paradoxical alterations on pain sensitivity","volume":"151","author":"AP Fernandez","year":"2010","journal-title":"Endocrinology"},{"issue":"8","key":"ref114","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/sj.onc.1206207","article-title":"Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by 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