{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:51:52Z","timestamp":1785909112965,"version":"3.56.0"},"reference-count":86,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008425","name":"Government of Galicia Department of Education Science Universities and Professional Training","doi-asserted-by":"publisher","award":["ED431B 2023\/25"],"award-info":[{"award-number":["ED431B 2023\/25"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018886","name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde","doi-asserted-by":"publisher","award":["2022.14060"],"award-info":[{"award-number":["2022.14060"]}],"id":[{"id":"10.13039\/501100018886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018886","name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde","doi-asserted-by":"publisher","award":["CEECIND\/CP1596\/CT0004"],"award-info":[{"award-number":["CEECIND\/CP1596\/CT0004"]}],"id":[{"id":"10.13039\/501100018886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018886","name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde","doi-asserted-by":"publisher","award":["2024.02245"],"award-info":[{"award-number":["2024.02245"]}],"id":[{"id":"10.13039\/501100018886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"State Agency of Research","doi-asserted-by":"publisher","award":["PID2021-124010OB-100"],"award-info":[{"award-number":["PID2021-124010OB-100"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2022.14060.BD"],"award-info":[{"award-number":["2022.14060.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2023.14440.PEX"],"award-info":[{"award-number":["2023.14440.PEX"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2020.02311.CEECIND\/CP1596\/CT0004"],"award-info":[{"award-number":["2020.02311.CEECIND\/CP1596\/CT0004"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["2024.02245.BD"],"award-info":[{"award-number":["2024.02245.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UI\/BD\/154888\/2023"],"award-info":[{"award-number":["UI\/BD\/154888\/2023"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UID\/50006\/2025"],"award-info":[{"award-number":["UID\/50006\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","em-consulte.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biomedicine &amp; Pharmacotherapy"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1016\/j.biopha.2026.119620","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:28:45Z","timestamp":1781245725000},"page":"119620","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Discovery of bridged melanostatin derivatives as potent allosteric modulators of the dopamine D2 receptors with improved permeability"],"prefix":"10.1016","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-6197","authenticated-orcid":false,"given":"Ivo E.","family":"Sampaio-Dias","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo F.","family":"Costa-Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1440-9873","authenticated-orcid":false,"given":"Xavier C.","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1464-7254","authenticated-orcid":false,"given":"Beatriz L.","family":"Pires-Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marialessandra","family":"Contino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5575-3240","authenticated-orcid":false,"given":"Giovanni","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Brea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddy","family":"Sotelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-5579","authenticated-orcid":false,"given":"Marco A.C.","family":"Preto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro N.","family":"Le\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2775-3147","authenticated-orcid":false,"given":"Ana","family":"Reis-Mendes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0471-2756","authenticated-orcid":false,"given":"Vera M.","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8922-8033","authenticated-orcid":false,"given":"Miguel A.","family":"Maestro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 E.","family":"Rodr\u00edguez-Borges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-6351","authenticated-orcid":false,"given":"Xerardo","family":"Garc\u00eda-Mera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.biopha.2026.119620_bib1","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1124\/jpet.105.091256","article-title":"Modulation of agonist binding to human dopamine receptor subtypes by l-prolyl-l-leucyl-glycinamide and a peptidomimetic analog","volume":"315","author":"Verma","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"10.1016\/j.biopha.2026.119620_bib2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0196-9781(80)90006-6","article-title":"Opiate receptor antagonism by l-prolyl-l-leucyl-glycinamide, MIF-I","volume":"1","author":"Dickinson","year":"1980","journal-title":"Peptides"},{"key":"10.1016\/j.biopha.2026.119620_bib3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0014-2999(79)90156-0","article-title":"Antagonism of morphine-induced catalepsy by l-prolyl-l-leucyl-glycinamide","volume":"53","author":"Chiu","year":"1979","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.biopha.2026.119620_bib4","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1016\/0024-3205(86)90391-7","article-title":"Existence of antiopiate systems as illustrated by MIF-1\/Tyr-MIF-1","volume":"39","author":"Galina","year":"1986","journal-title":"Life Sci."},{"key":"10.1016\/j.biopha.2026.119620_bib5","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/0196-9781(82)90055-9","article-title":"Inhibition by l-prolyl-l-leucyl-glycinamide (PLG) of alpha-melanocyte stimulating hormone release from hypothalamic slices","volume":"3","author":"Scimonelli","year":"1982","journal-title":"Peptides"},{"key":"10.1016\/j.biopha.2026.119620_bib6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3109\/00207459008994244","article-title":"MIF-induced augmentation of melatonin functions: possible relevance to mechanisms of action of MIF-1 in movement disorders","volume":"52","author":"Sandyk","year":"1990","journal-title":"Int. J. Neurosci."},{"key":"10.1016\/j.biopha.2026.119620_bib7","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/j.1471-4159.1988.tb03005.x","article-title":"Interaction of l-prolyl-l-leucyl glycinamide with dopamine D2 receptor: evidence for modulation of agonist affinity states in bovine striatal membranes","volume":"50","author":"Srivastava","year":"1988","journal-title":"J. Neurochem."},{"key":"10.1016\/j.biopha.2026.119620_bib8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrd2760","article-title":"Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders","volume":"8","author":"Conn","year":"2009","journal-title":"Nat. Rev. Drug. Discov."},{"key":"10.1016\/j.biopha.2026.119620_bib9","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1021\/acs.jmedchem.8b00875","article-title":"Allosteric modulation of class A GPCRs: targets, agents, and emerging concepts","volume":"62","author":"Wold","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib10","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/sj.mp.4001507","article-title":"Dopamine in drug abuse and addiction: results from imaging studies and treatment implications","volume":"9","author":"Volkow","year":"2004","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.biopha.2026.119620_bib11","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.1038\/s41598-023-31250-2","article-title":"Striatal dopamine D2-like receptors availability in obesity and its modulation by bariatric surgery: a systematic review and meta-analysis","volume":"13","author":"Ribeiro","year":"2023","journal-title":"Sci. Rep."},{"key":"10.1016\/j.biopha.2026.119620_bib12","article-title":"Dopamine receptors: is it possible to become a therapeutic target for depression?","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.biopha.2026.119620_bib13","first-page":"303","article-title":"Melanocyte-stimulating-hormone release-inhibiting factor-I and tardive dyskinesia","volume":"38","author":"Ehrensing","year":"1977","journal-title":"Dis. Nerv. Syst."},{"key":"10.1016\/j.biopha.2026.119620_bib14","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2047-9158-1-6","article-title":"Linking restless legs syndrome with Parkinson's disease: clinical, imaging and genetic evidence","volume":"1","author":"Peeraully","year":"2012","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.biopha.2026.119620_bib15","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2019.22360","article-title":"Diagnosis and treatment of Parkinson disease: a review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"10.1016\/j.biopha.2026.119620_bib16","doi-asserted-by":"crossref","first-page":"832","DOI":"10.12968\/bjon.1998.7.14.5636","article-title":"Role of dopamine in schizophrenia and Parkinson's disease","volume":"7","author":"Birtwistle","year":"1998","journal-title":"Br. J. Nurs."},{"key":"10.1016\/j.biopha.2026.119620_bib17","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0306-3623(82)90090-8","article-title":"The effects of prolyl-leucyl-glycine amide on drug-induced rotation in lesioned rats","volume":"13","author":"Smith","year":"1982","journal-title":"Gen. Pharmacol."},{"key":"10.1016\/j.biopha.2026.119620_bib18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0196-9781(97)00321-5","article-title":"Protection against MPTP treatment by an analog of Pro-Leu-Gly-NH2 (PLG, MIF-1)","volume":"19","author":"Marcotte","year":"1998","journal-title":"Peptides"},{"key":"10.1016\/j.biopha.2026.119620_bib19","first-page":"120","article-title":"Double-blind evaluation of oral L-prolyl-L-leucyl-glycine amide in Parkinson's disease","volume":"114","author":"Barbeau","year":"1976","journal-title":"Can. Med. Assoc. J."},{"key":"10.1016\/j.biopha.2026.119620_bib20","first-page":"1079","article-title":"Preliminary clinical studies with l-prolyl-l-leucyl-glycine amide in Parkinson's disease","volume":"107","author":"Kastin","year":"1972","journal-title":"Can. Med. Assoc. J."},{"key":"10.1016\/j.biopha.2026.119620_bib21","first-page":"360","article-title":"Effect of melanocyte-stimulating hormone-release inhibiting factor (MIF) in Parkinson\u2019s syndrom","volume":"12","author":"Fischer","year":"1974","journal-title":"Eur. Neurol."},{"key":"10.1016\/j.biopha.2026.119620_bib22","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S0140-6736(75)90778-3","article-title":"Potentiation of levodopa effect by intravenous l-prolyl-l-leucyl-glycine amide in man","volume":"306","author":"Barbeau","year":"1975","journal-title":"Lancet"},{"key":"10.1016\/j.biopha.2026.119620_bib23","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1021\/jo302368y","article-title":"Chirality-driven folding of short \u03b2-lactam pseudopeptides","volume":"78","author":"Aizpurua","year":"2013","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib24","doi-asserted-by":"crossref","first-page":"7523","DOI":"10.1021\/ja00803a062","article-title":"Solid state conformation of the C-terminal tripeptide of oxytocin, l-Pro-l-Leu-Gly-NH2.0.5H2O","volume":"95","author":"Reed","year":"1973","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.biopha.2026.119620_bib25","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1039\/b718058f","article-title":"Synthesis and evaluation of novel pyridine based PLG tripeptidomimetics","volume":"6","author":"Saitton","year":"2008","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib26","doi-asserted-by":"crossref","first-page":"6595","DOI":"10.1021\/jm049484q","article-title":"Design, synthesis and evaluation of a PLG tripeptidomimetic based on a pyridine scaffold","volume":"47","author":"Saitton","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib27","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1021\/acschemneuro.9b00259","article-title":"Synthesis, pharmacological, and biological evaluation of MIF-1 picolinoyl peptidomimetics as positive allosteric modulators of D2R","volume":"10","author":"Sampaio-Dias","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.biopha.2026.119620_bib28","doi-asserted-by":"crossref","first-page":"6209","DOI":"10.1021\/acs.jmedchem.1c00252","article-title":"Discovery of new potent positive allosteric modulators of dopamine D2 receptors: insights into the bioisosteric replacement of proline to 3-furoic acid in the melanostatin neuropeptide","volume":"64","author":"Sampaio-Dias","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/nature25758","article-title":"Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone","volume":"555","author":"Wang","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.biopha.2026.119620_bib30","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/s41467-020-14884-y","article-title":"Haloperidol bound D2 dopamine receptor structure inspired the discovery of subtype selective ligands","volume":"11","author":"Fan","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.biopha.2026.119620_bib31","doi-asserted-by":"crossref","first-page":"6442","DOI":"10.1038\/s41467-020-20221-0","article-title":"Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone","volume":"11","author":"Im","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.biopha.2026.119620_bib32","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1021\/jm050644n","article-title":"Design and synthesis of photoaffinity-labeling ligands of the l-prolyl-l-leucylglycinamide binding site involved in the allosteric modulation of the dopamine receptor","volume":"49","author":"Fisher","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2026.119091","article-title":"Discovery of first-in-class melanostatin-based ago-allosteric modulators of the dopamine D2 receptors","volume":"196","author":"Costa-Almeida","year":"2026","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.biopha.2026.119620_bib34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1124\/mol.115.100172","article-title":"In vitro and in vivo identification of novel positive allosteric modulators of the human dopamine D2 and D3 receptor","volume":"89","author":"Wood","year":"2016","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.biopha.2026.119620_bib35","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s43440-021-00352-x","article-title":"Allosteric modulation of dopamine D2L receptor in complex with Gi1 and Gi2 proteins: the effect of subtle structural and stereochemical ligand modifications","volume":"74","author":"\u017buk","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"10.1016\/j.biopha.2026.119620_bib36","doi-asserted-by":"crossref","DOI":"10.1002\/cmdc.202100681","article-title":"Synthesis of bitopic ligands as potent dopamine D2 receptor agonists","volume":"17","author":"Qian","year":"2022","journal-title":"ChemMedChem"},{"key":"10.1016\/j.biopha.2026.119620_bib37","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.1039\/C9MD00379G","article-title":"Talipexole variations as novel bitopic dopamine D2 and D3 receptor ligands","volume":"10","author":"Stank","year":"2019","journal-title":"MedChemComm"},{"key":"10.1016\/j.biopha.2026.119620_bib38","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1021\/acschemneuro.0c00687","article-title":"Synthesis, pharmacological, and biological evaluation of 2-furoyl-based MIF-1 peptidomimetics and the development of a general-purpose model for allosteric modulators (ALLOPTML)","volume":"12","author":"Sampaio-Dias","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.biopha.2026.119620_bib39","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1021\/acsmedchemlett.5c00287","article-title":"Proline homologation in melanostatin neuropeptide: discovery of potent modulators of the dopamine D2 receptors","volume":"16","author":"Sampaio-Dias","year":"2025","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib40","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1021\/acsmedchemlett.3c00264","article-title":"Stapling amantadine to melanostatin neuropeptide: discovery of potent positive allosteric modulators of the D2 receptors","volume":"14","author":"Silva-Reis","year":"2023","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib41","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ejmech.2013.08.001","article-title":"Synthesis and allosteric modulation of the dopamine receptor by peptide analogs of l-prolyl-l-leucyl-glycinamide (PLG) modified in the l-proline or l-proline and l-leucine scaffolds","volume":"69","author":"Ferreira da Costa","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib42","doi-asserted-by":"crossref","first-page":"11065","DOI":"10.1039\/C6OB02248K","article-title":"Novel l-prolyl-l-leucylglycinamide (PLG) tripeptidomimetics based on a 2-azanorbornane scaffold as positive allosteric modulators of the D2R","volume":"14","author":"Sampaio-Dias","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib43","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1021\/jm00160a052","article-title":"Synthesis of Pro-Leu-Gly-NH2 analogues modified at the prolyl residue and evaluation of their effects on the receptor binding activity of the central dopamine receptor agonist, ADTN","volume":"29","author":"Johnson","year":"1986","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib44","doi-asserted-by":"crossref","first-page":"3615","DOI":"10.1021\/acschemneuro.1c00339","article-title":"Design, synthesis, and biological evaluation of hybrid glypromate analogues using 2-azanorbornane as a prolyl and pipecolyl surrogate","volume":"12","author":"Sampaio-Dias","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.biopha.2026.119620_bib45","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1016\/j.bmcl.2005.12.046","article-title":"Novel inhibitors of hepatitis C NS3-NS4A serine protease derived from 2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid","volume":"16","author":"Venkatraman","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib46","doi-asserted-by":"crossref","first-page":"3711","DOI":"10.1039\/D4MD00584H","article-title":"Discovery of hybrid Glypromate conjugates with neuroprotective activity against paraquat-induced toxicity","volume":"15","author":"Silva-Reis","year":"2024","journal-title":"RSC Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib47","doi-asserted-by":"crossref","first-page":"6116","DOI":"10.1039\/C5OB00173K","article-title":"2-Azanorbornane \u2013 a versatile chiral aza-Diels\u2013Alder cycloadduct: preparation, applications in stereoselective synthesis and biological activity","volume":"13","author":"Wojaczy\u0144ska","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib48","doi-asserted-by":"crossref","first-page":"6546","DOI":"10.1021\/acs.orglett.4c02013","article-title":"Diastereoselective [3 + 2] cycloaddition between tertiary amine N-oxides and substituted alkenes to access 7-azanorbornanes","volume":"26","author":"Cocolas","year":"2024","journal-title":"Org. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib49","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1016\/S0960-894X(03)00758-3","article-title":"Synthesis and evaluation of chiral bicyclic proline FKBP12 ligands","volume":"13","author":"Limburg","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib50","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0957-4166(02)00048-4","article-title":"An improved synthesis of enantiopure 2-azabicyclo[2.2.1]heptane-3-carboxylic acid","volume":"13","author":"Tararov","year":"2002","journal-title":"Tetrahedron Asymmetry"},{"key":"10.1016\/j.biopha.2026.119620_bib51","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1021\/acschemneuro.8b00083","article-title":"Perturbation theory\/machine learning model of ChEMBL data for dopamine targets: docking, synthesis, and assay of new l-prolyl-l-leucyl-glycinamide peptidomimetics","volume":"9","author":"Ferreira da Costa","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.biopha.2026.119620_bib52","doi-asserted-by":"crossref","first-page":"3540","DOI":"10.1039\/C9QO00957D","article-title":"Mechanistic insights for the transprotection of tertiary amines with Boc2O via charged carbamates: access to both enantiomers of 2-azanorbornane-3-exo-carboxylic acids","volume":"6","author":"Sampaio-Dias","year":"2019","journal-title":"Org. Chem. Front."},{"key":"10.1016\/j.biopha.2026.119620_bib53","doi-asserted-by":"crossref","first-page":"7533","DOI":"10.1039\/C7OB01544E","article-title":"Highly efficient one-pot assembly of peptides by double chemoselective coupling","volume":"15","author":"Sampaio-Dias","year":"2017","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib54","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1055\/a-1695-1095","article-title":"A Convenient on-site oxidation strategy for the N-hydroxylation of melanostatin neuropeptide using Cope elimination","volume":"54","author":"Sampaio-Dias","year":"2022","journal-title":"Synthesis"},{"key":"10.1016\/j.biopha.2026.119620_bib55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-394587-7.00001-4","article-title":"Approaches for probing allosteric interactions at 7 transmembrane spanning receptors","volume":"115","author":"Klein","year":"2013","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"10.1016\/j.biopha.2026.119620_bib56","unstructured":"Open-source cheminformatics, \u3008http:\/\/zinc15.docking.org\/patterns\/home\u3009 (accessed 2025-02-13)."},{"key":"10.1016\/j.biopha.2026.119620_bib57","series-title":"Drug-Induced Liver Toxicity","first-page":"151","article-title":"Use of liver-derived cell lines for the study of drug-induced liver injury","author":"Ren","year":"2018"},{"key":"10.1016\/j.biopha.2026.119620_bib58","first-page":"1286","article-title":"The rediscovery of HepG2 cells for prediction of drug induced liver injury (DILI)","volume":"13","author":"Ghallab","year":"2014","journal-title":"EXCLI J."},{"key":"10.1016\/j.biopha.2026.119620_bib59","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.toxlet.2012.11.015","article-title":"Neurotoxicity of \"ecstasy\" and its metabolites in human dopaminergic differentiated SH-SY5Y cells","volume":"216","author":"Ferreira","year":"2013","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.biopha.2026.119620_bib60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y cell line in Parkinson\u2019s disease research: a systematic review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.biopha.2026.119620_bib61","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/BF03033178","article-title":"Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists","volume":"5","author":"Presgraves","year":"2003","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.biopha.2026.119620_bib62","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00204-013-1120-7","article-title":"The mixture of \"ecstasy\" and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations","volume":"88","author":"Barbosa","year":"2014","journal-title":"Arch. Toxicol."},{"key":"10.1016\/j.biopha.2026.119620_bib63","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1111\/j.1471-4159.2007.05115.x","article-title":"6-Hydroxydopamine activates the mitochondrial apoptosis pathway through p38 MAPK-mediated, p53-independent activation of Bax and PUMA","volume":"104","author":"Gomez-Lazaro","year":"2008","journal-title":"J. Neurochem."},{"issue":"2","key":"10.1016\/j.biopha.2026.119620_bib64","doi-asserted-by":"crossref","first-page":"S124","DOI":"10.1016\/j.parkreldis.2008.04.015","article-title":"The 6-hydroxydopamine model: News from the past","volume":"14","author":"Blandini","year":"2008","journal-title":"Relat. Disord."},{"key":"10.1016\/j.biopha.2026.119620_bib65","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.neuroscience.2013.02.030","article-title":"Protective effect of creatine against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells: involvement of intracellular signaling pathways","volume":"238","author":"Cunha","year":"2013","journal-title":"Neurosci"},{"key":"10.1016\/j.biopha.2026.119620_bib66","article-title":"Regulated expression of lentivirus-mediated GDNF in human bone marrow-derived mesenchymal stem cells and its neuroprotection on dopaminergic cells in vitro","volume":"8","author":"Yang","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.biopha.2026.119620_bib67","doi-asserted-by":"crossref","first-page":"31","DOI":"10.4236\/pp.2013.41004","article-title":"Aged garlic extract reduces ROS production and cell death induced by 6-hydroxydopamine through activation of the Nrf2-ARE pathway in SH-SY5Y cells","volume":"4","author":"Kohda","year":"2013","journal-title":"Pharmacol. Pharm."},{"key":"10.1016\/j.biopha.2026.119620_bib68","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112843","article-title":"One molecule two goals: A selective P-glycoprotein modulator increases drug transport across gastro-intestinal barrier and recovers doxorubicin toxicity in multidrug resistant cancer cells","volume":"208","author":"Contino","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib69","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1002\/cmdc.201700239","article-title":"Structure-activity relationship studies on 6,7-dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline derivatives as multidrug resistance reversers","volume":"12","author":"Teodori","year":"2017","journal-title":"ChemMedChem"},{"key":"10.1016\/j.biopha.2026.119620_bib70","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3390\/ph17010135","article-title":"Harmaline to human mitochondrial caseinolytic serine protease activation for pediatric diffuse intrinsic pontine glioma treatment","volume":"17","author":"Miciaccia","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.biopha.2026.119620_bib71","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/bdd.2345","article-title":"Recent advances in the in vitro and in vivo methods to assess impact of P-glycoprotein and breast cancer resistance protein transporters in central nervous system drug disposition","volume":"44","author":"Chatterjee","year":"2023","journal-title":"Biopharm. Drug. Dispos."},{"key":"10.1016\/j.biopha.2026.119620_bib72","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1124\/dmd.104.003442","article-title":"Expression, localization, and functional characteristics of breast cancer resistance protein in Caco-2 cells","volume":"33","author":"Xia","year":"2005","journal-title":"Drug. Metab. Dispos."},{"key":"10.1016\/j.biopha.2026.119620_bib73","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/S0005-2736(99)00169-8","article-title":"Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance","volume":"1461","author":"K\u00f6nig","year":"1999","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.biopha.2026.119620_bib74","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3390\/pharmaceutics13071103","article-title":"Pharmaceutical formulations with P-glycoprotein inhibitory effect as promising approaches for enhancing oral drug absorption and bioavailability","volume":"13","author":"Nguyen","year":"2021","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.biopha.2026.119620_bib75","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1002\/mdc3.14056","article-title":"Levodopa-induced dyskinesias are frequent and impact quality of life in Parkinson's disease: a 5-year follow-up study","volume":"11","author":"Santos-Garc\u00eda","year":"2024","journal-title":"Mov. Disord. Clin. Pract."},{"key":"10.1016\/j.biopha.2026.119620_bib76","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/0005-2795(80)90075-6","article-title":"Laser Raman studies on the conformation of Pro-Leu-Gly-NH2","volume":"624","author":"Hseu","year":"1980","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.biopha.2026.119620_bib77","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1021\/jm00074a032","article-title":"Dopamine receptor modulation by a highly rigid spiro bicyclic peptidomimetic of Pro-Leu-Gly-NH2","volume":"36","author":"Genin","year":"1993","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib78","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1021\/jm00054a010","article-title":"Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogs of Pro-Leu-Gly-NH2","volume":"36","author":"Sreenivasan","year":"1993","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib79","doi-asserted-by":"crossref","first-page":"2356","DOI":"10.1021\/jm00068a013","article-title":"Bicyclic thiazolidine lactam peptidomimetics of the dopamine receptor modulating peptide Pro-Leu-Gly-NH2","volume":"36","author":"Subasinghe","year":"1993","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib80","doi-asserted-by":"crossref","first-page":"3677","DOI":"10.1021\/jm00048a003","article-title":"X-ray analysis, and dopamine receptor-modulating activity of mimics of the \"C5\" hydrogen-bonded conformation in the peptidomimetic 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacetamide","volume":"37","author":"Baures","year":"1994","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib81","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1021\/jm980656r","article-title":"Synthesis and dopamine receptor modulating activity of novel peptidomimetics of l-prolyl-l-leucyl-glycinamide featuring \u03b1,\u03b1-disubstituted amino acids","volume":"42","author":"Evans","year":"1999","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib82","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/jo971176v","article-title":"NMR chemical shifts of common laboratory solvents as trace impurities","volume":"62","author":"Gottlieb","year":"1997","journal-title":"J. Org. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib83","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3390\/ph11020041","article-title":"Mitoxantrone is more toxic than doxorubicin in SH-SY5Y human cells: a 'chemobrain' in vitro study","volume":"11","author":"Almeida","year":"2018","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.biopha.2026.119620_bib84","doi-asserted-by":"crossref","first-page":"9983","DOI":"10.1021\/jm501640e","article-title":"SAR Studies on tetrahydroisoquinoline derivatives: the role of flexibility and bioisosterism to raise potency and selectivity toward P-glycoprotein","volume":"57","author":"Capparelli","year":"2014","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.biopha.2026.119620_bib85","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1177\/2211068214561025","article-title":"TEER measurement techniques for in vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J. Lab. Autom."},{"key":"10.1016\/j.biopha.2026.119620_bib86","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.bmc.2012.12.021","article-title":"Naphthalenyl derivatives for hitting P-gp\/MRP1\/BCRP transporters","volume":"21","author":"Colabufo","year":"2013","journal-title":"Bioorg. Med. Chem."}],"container-title":["Biomedicine &amp; Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226006566?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0753332226006566?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:37:33Z","timestamp":1785908253000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0753332226006566"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":86,"alternative-id":["S0753332226006566"],"URL":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119620","relation":{},"ISSN":["0753-3322"],"issn-type":[{"value":"0753-3322","type":"print"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of bridged melanostatin derivatives as potent allosteric modulators of the dopamine D2 receptors with improved permeability","name":"articletitle","label":"Article Title"},{"value":"Biomedicine & Pharmacotherapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.biopha.2026.119620","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Author(s). Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"119620"}}