{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:22:21Z","timestamp":1788744141418,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T00:00:00Z","timestamp":1694649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Calcitonin gene\u2010related peptide (CGRP) is involved in migraine pathophysiology. CGRP can signal through two receptors. The canonical CGRP receptor comprises the calcitonin receptor\u2010like receptor and receptor activity\u2010modifying protein 1 (RAMP1); the AMY<jats:sub>1<\/jats:sub> receptor comprises the calcitonin receptor with RAMP1. Drugs that reduce CGRP activity, such as receptor antagonists, are approved for the treatment and prevention of migraine. Despite being designed to target the canonical CGRP receptor, emerging evidence suggests that these antagonists, including erenumab (a monoclonal antibody antagonist) can also antagonise the AMY<jats:sub>1<\/jats:sub> receptor. However, it is difficult to estimate its selectivity because direct comparisons between receptors under matched conditions have not been made. We therefore characterised erenumab at both CGRP\u2010responsive receptors with multiple ligands, including \u03b1CGRP and \u03b2CGRP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Erenumab antagonism was quantified through IC<jats:sub>50<\/jats:sub> and pK<jats:sub>B<\/jats:sub> experiments, measuring cAMP production. We used SK\u2010N\u2010MC cells which endogenously express the human CGRP receptor, and HEK293S and Cos7 cells transiently transfected to express either human CGRP or AMY<jats:sub>1<\/jats:sub> receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Erenumab antagonised both the CGRP and AMY<jats:sub>1<\/jats:sub> receptors with an ~20\u2013120\u2010fold preference for the CGRP receptor, depending on the cells, agonist, analytical approach and\/or assay format. Erenumab antagonised both forms of CGRP equally, and appeared to act as a competitive reversible antagonist at both receptors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Despite being designed to target the CGRP receptor, erenumab can antagonise the AMY<jats:sub>1<\/jats:sub> receptor. Its ability to antagonise CGRP activity at both receptors may be useful in better understanding the clinical profile of erenumab.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16218","type":"journal-article","created":{"date-parts":[[2023,8,15]],"date-time":"2023-08-15T04:10:57Z","timestamp":1692072657000},"page":"142-161","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Pharmacological characterisation of erenumab, Aimovig, at two calcitonin gene\u2010related peptide responsive receptors"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5332-1236","authenticated-orcid":false,"given":"Michael L.","family":"Garelja","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6396-6521","authenticated-orcid":false,"given":"Tyla I.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-7994","authenticated-orcid":false,"given":"Amy","family":"Bennie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3351-0897","authenticated-orcid":false,"given":"Mhairi","family":"Nimick","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1051-7770","authenticated-orcid":false,"given":"Jakeb","family":"Petersen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8151-4123","authenticated-orcid":false,"given":"Christopher S.","family":"Walker","sequence":"additional","affiliation":[{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland  Auckland New Zealand"},{"name":"School of Biological Sciences University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-5122","authenticated-orcid":false,"given":"Debbie L.","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Otago  Dunedin New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13956"},{"issue":"1","key":"e_1_2_13_3_1","first-page":"S27","article-title":"THE CONCISE GUIDE TO PHARMACOLOGY 2021\/22: G protein\u2010coupled receptors","volume":"178","author":"Alexander S. P.","year":"2021","journal-title":"British Journal of Pharmacology"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00032"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.11.014"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1713074114"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.10.012"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420983282"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.8b00002"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.05.021"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704761"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.56.1.235"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28204-z"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0003-1"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-12-112"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.024042"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.029"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15628"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15585"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26072"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011930"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.05.014"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-022-01425-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00879.x"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.104.008615"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.106.027953"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14075"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024221084029"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.799"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.832589"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14336"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-018-0009-5"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-407663-1.00006-5"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00310.x"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.1c00135"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)89066-5"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.9b00080"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-0992-1"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/30666"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/oso\/9780195171792.001.0001"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008944"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.4.4"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419867282"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01240"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.08.014"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.54.2.233"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.047142"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02197.x"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.426288"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.860037"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00059.2021"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.130344"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.163816"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01323-6"},{"key":"e_1_2_13_57_1","unstructured":"Schr\u00f6dinger L. &DeLano W.(2020).PyMOL."},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-022-01171-5"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.227793"},{"key":"e_1_2_13_60_1","first-page":"61","article-title":"Amylin receptor phenotypes derived from human calcitonin receptor\/RAMP coexpression exhibit pharmacological differences dependent on receptor isoform and host cell environment","volume":"294","author":"Tilakaratne N.","year":"2000","journal-title":"The Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.197"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417691762"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2017.07.005"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.042283"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706997"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706656114"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T09:55:55Z","timestamp":1703066155000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,14]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/bph.16218"],"URL":"https:\/\/doi.org\/10.1111\/bph.16218","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,14]]},"assertion":[{"value":"2023-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}