{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T20:04:45Z","timestamp":1770062685741,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Polyphenol ellagic acid (EA) possesses antioxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, making it an interesting multi-targeting profile. EA also controls the central nervous system (CNS), since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human \u03b12A-ARs and \u03b12C-AR catalytic pockets, comparing EA behaviour with that of known agonists and antagonists. Structurally, the hydrophobic residues surrounding the \u03b12A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the \u03b12A-AR, with respect to \u03b12C-AR. Moreover, EA seems to better accommodate within \u03b12A-ARs into the TM5 area, close to S200 and S204, which play a crucial role for activation of aminergic GPCRs such as the \u03b12-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in a yohimbine-sensitive fashion that confirms the engagement of na\u00efve \u03b12-ARs in the EA-mediated effect.<\/jats:p>","DOI":"10.3390\/antiox10111759","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T09:11:32Z","timestamp":1636017092000},"page":"1759","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Presynaptic Release-Regulating Alpha2 Autoreceptors: Potential Molecular Target for Ellagic Acid Nutraceutical Properties"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-7863","authenticated-orcid":false,"given":"Isabella","family":"Romeo","sequence":"first","affiliation":[{"name":"Net4Science Academic Spin-Off, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Associazione CRISEA\u2014Centro di Ricerca e Servizi Avanzati per l\u2019Innovazione Rurale, Localit\u00e0 Condoleo, 88055 Belcastro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Vallarino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-0026","authenticated-orcid":false,"given":"Federica","family":"Turrini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Roggeri","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guendalina","family":"Olivero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7043-4555","authenticated-orcid":false,"given":"Raffaella","family":"Boggia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Alcaro","sequence":"additional","affiliation":[{"name":"Net4Science Academic Spin-Off, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Associazione CRISEA\u2014Centro di Ricerca e Servizi Avanzati per l\u2019Innovazione Rurale, Localit\u00e0 Condoleo, 88055 Belcastro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-9479","authenticated-orcid":false,"given":"Giosu\u00e8","family":"Costa","sequence":"additional","affiliation":[{"name":"Net4Science Academic Spin-Off, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi \u201cMagna Gr\u00e6cia\u201d di Catanzaro, Campus \u201cS. Venuta\u201d, Viale Europa, 88100 Catanzaro, Italy"},{"name":"Associazione CRISEA\u2014Centro di Ricerca e Servizi Avanzati per l\u2019Innovazione Rurale, Localit\u00e0 Condoleo, 88055 Belcastro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-1165","authenticated-orcid":false,"given":"Anna","family":"Pittaluga","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, 16145 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.jpba.2018.12.033","article-title":"Isolation of punicalagin from Punica granatum rind extract using mass-directed semi-preparative ESI-AP single quadrupole LC-MS","volume":"166","author":"Barbieri","year":"2019","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Turrini, F., Malaspina, P., Giordani, P., Catena, S., Zunin, P., and Boggia, R. (2020). Traditional decoction and PUAE aqueous extracts of pomegranate peels as potential anti-tyrosinase ingredients. Appl. Sci., 10.","DOI":"10.3390\/app10082795"},{"key":"ref_3","unstructured":"(2020, November 17). Global Pomegranate Market Industry Trends, Sales, Supply, Demand, Analysis & Forecast. Available online: https:\/\/www.researchmoz.us\/global-pomegranate-market-2017-industry-trends-sales-supply-demand-analysis-and-forecast-to-2022-report.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"128302","DOI":"10.1016\/j.foodchem.2020.128302","article-title":"Chemical and physical attributes of fruit juice and peel of pomegranate genotypes grown in Florida USA","volume":"342","author":"Shahkoomahally","year":"2020","journal-title":"Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ifeanyichukwu, U.L., Fayemi, O.E., and Ateba, C.N. (2020). Green Synthesis of Zinc Oxide Nanoparticles from Pomegranate (Punica granatum) Extracts and Characterization of Their Antibacterial Activity. Molecules, 25.","DOI":"10.3390\/molecules25194521"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zuccari, G., Baldassari, S., Ailuno, G., Turrini, F., Alfei, S., and Caviglioli, G. (2020). Formulation strategies to improve oral bioavailability of ellagic acid. Appl. Sci., 10.","DOI":"10.20944\/preprints202004.0100.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.2174\/1381612822666160125114503","article-title":"Insights into Effects of Ellagic Acid on the Nervous System: A Mini Review","volume":"22","author":"Ahmed","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111724","DOI":"10.1016\/j.ejmech.2019.111724","article-title":"Ellagic Acid a multi-target bioactive compound for drug discovery in CNS? A narrative review","volume":"183","author":"Alfei","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Boggia, R., Turrini, F., Roggeri, A., Olivero, G., Cisani, F., Bonfiglio, T., Summa, M., Grilli, M., Caviglioli, G., and Alfei, S. (2020). Neuroinflammation in Aged Brain: Impact of the Oral Administration of Ellagic Acid Microdispersion. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21103631"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Magangana, T.P., Makunga, N.P., Fawole, O.A., and Opara, U.L. (2020). Processing Factors Affecting the Phytochemical and Nutritional Properties of Pomegranate (Punica granatum L.) Peel Waste: A Review. Molecules, 25.","DOI":"10.3390\/molecules25204690"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00217-019-03339-4","article-title":"From pomegranate marcs to a potential bioactive ingredient: A recycling proposal for pomegranate-squeezed marcs","volume":"246","author":"Turrini","year":"2020","journal-title":"Europ. Food Res. Technol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.fbp.2019.06.014","article-title":"Traditional or hydro-diffusion and gravity microwave coupled with ultrasound as green technologies for the valorization of pomegranate external peels","volume":"117","author":"Turrini","year":"2019","journal-title":"Food Bioprod. Process."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ejmech.2019.01.023","article-title":"A novel cereblon modulator for targeted protein degradation","volume":"15","author":"Kim","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1055\/a-0633-9492","article-title":"A Pharmacological Update of Ellagic Acid","volume":"84","author":"Giner","year":"2018","journal-title":"Planta Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1872213X12666180221154713","article-title":"The Promising Pharmacological Effects and Therapeutic\/Medicinal Applications of Punica granatum L. (Pomegranate) as a Functional Food in Humans and Animals","volume":"12","author":"Saeed","year":"2018","journal-title":"Recent Pat. Inflamm. Allergy Drug Discov."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1007\/s11064-016-1853-9","article-title":"The Effects of Ellagic Acid upon Brain Cells: A Mechanistic View and Future Directions","volume":"41","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejphar.2012.02.034","article-title":"Evidence for the involvement of the monoaminergic system, but not the opioid system in the antidepressant-like activity of ellagic acid in mice","volume":"682","author":"Girish","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"754","DOI":"10.3181\/00379727-132-34303","article-title":"The mechanism of blood pressure depression by ellagic acid","volume":"132","author":"Bhargava","year":"1969","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1007\/s00210-003-0829-x","article-title":"All three alpha2-adrenoceptor types serve as autoreceptors in postganglionic sympathetic neurons","volume":"368","author":"Trendelenburg","year":"2003","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.neuint.2007.04.031","article-title":"Presynaptic autoreceptors regulating transmitter release","volume":"52","author":"Langer","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4875","DOI":"10.1523\/JNEUROSCI.21-13-04875.2001","article-title":"The \u03b12A-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety","volume":"21","author":"Schramm","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuropharm.2007.04.006","article-title":"Antidepressant treatments and function of glutamate ionotropic receptors mediating amine release in hippocampus","volume":"53","author":"Pittaluga","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.neuint.2003.11.016","article-title":"Nonsynaptic Communication in the Central Nervous System","volume":"45","author":"Vizi","year":"2004","journal-title":"Neurochem. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109987","DOI":"10.1016\/j.pnpbp.2020.109987","article-title":"Triple reuptake inhibition of serotonin, norepinephrine, and dopamine increases the tonic activation of \u03b12-adrenoceptors in the rat hippocampus and dopamine levels in the nucleus accumbens","volume":"103","author":"Jiang","year":"2020","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Giorgi, F.S., Biagioni, F., Galgani, A., Pavese, N., Lazzeri, G., and Fornai, F. (2020). Locus Coeruleus Modulates Neuroinflammation in Parkinsonism and Dementia. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228630"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/0165-6147(91)90499-I","article-title":"Molecular characterization of alpha 1- and alpha 2-adrenoceptors","volume":"12","author":"Harrison","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s002100100423","article-title":"A study of presynaptic \u03b12-autoreceptors in \u03b12A\/D-, \u03b12B- and \u03b12C-adrenoceptor-deficient mice","volume":"364","author":"Trendelenburg","year":"2001","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.neuropharm.2018.01.026","article-title":"Environmental training is beneficial to clinical symptoms and cortical presynaptic defects in mice suffering from experimental autoimmune encephalomyelitis","volume":"145","author":"Bonfiglio","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.neuint.2007.06.001","article-title":"Role of Nonsynaptic Communication in Regulating the Immune Response","volume":"52","author":"Selmeczy","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1017\/S146114570800967X","article-title":"Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: Implications for depression and neurodegeneration","volume":"12","author":"Ryan","year":"2009","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jneuroim.2009.12.007","article-title":"Noradrenaline reuptake inhibitors inhibit expression of chemokines IP-10 and RANTES and cell adhesion molecules VCAM-1 and ICAM-1 in the CNS following a systemic inflammatory challenge","volume":"220","author":"Ryan","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0197-0186(02)00049-9","article-title":"Noradrenergic regulation of inflammatory gene expression in brain","volume":"41","author":"Feinstein","year":"2002","journal-title":"Neurochem. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1196\/annals.1391.026","article-title":"The catecholamine cytokine balance: Interaction between the brain and the immune system","volume":"1113","author":"Vizi","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_34","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: Maestro, Schr\u00f6dinger LLC."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.bbrc.2018.01.160","article-title":"Predicting ligand binding poses for low-resolution membrane protein models: Perspectives from multiscale simulations","volume":"498","author":"Schneider","year":"2018","journal-title":"Biochem. Biophys. Res. Comm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1016\/j.celrep.2019.10.088","article-title":"Structural basis of the diversity of adrenergic receptors","volume":"29","author":"Qu","year":"2019","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chen, X.Y., Wu, D., Wu, L.J., Han, G.W., Guo, Y., and Zhong, G.S. (2019). Crystal structure of human alpha2C adrenergic G protein-coupled receptor. Released Protein Data Bank.","DOI":"10.2210\/pdb6kuw\/pdb"},{"key":"ref_38","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: Protein Preparation Wizard, Schr\u00f6dinger LLC."},{"key":"ref_39","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: Epik, Schr\u00f6dinger LLC."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_42","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: LigPrep, Schr\u00f6dinger LLC."},{"key":"ref_43","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: Glide, Schr\u00f6dinger LLC."},{"key":"ref_44","unstructured":"(2018). Schr\u00f6dinger Release 2018-1: Desmond Molecular Dynamics System, D.E. Shaw Research."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D370","DOI":"10.1093\/nar\/gkr703","article-title":"OPM database and PPM web server: Resources for positioning of proteins in membranes","volume":"40","author":"Lomize","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, D.E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the SC \u201806: Proceedings of the 2006 ACM\/IEEE Conference on Supercomputing 2006, Tampa, FL, USA.","DOI":"10.1145\/1188455.1188544"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1016\/j.celrep.2019.10.112","article-title":"Molecular Mechanism for Ligand Recognition and Subtype Selectivity of \u03b12C Adrenergic Receptor","volume":"29","author":"Chen","year":"2019","journal-title":"Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112947","DOI":"10.1016\/j.ejmech.2020.112947","article-title":"Di-aryl guanidinium derivatives: Towards improved \u03b12-Adrenergic affinity and antagonist activity","volume":"209","author":"McMullan","year":"2021","journal-title":"Europ. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Model."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1002\/jcc.22933","article-title":"Influence of the solvent representation on vibrational entropy calculations: Generalized Born versus distance-dependent dielectric model","volume":"12","author":"Kopitz","year":"2012","journal-title":"J. Comput. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1517\/17460441.2015.1032936","article-title":"The MM\/PBSA and MM\/GBSA methods to estimate ligand-binding affinities","volume":"10","author":"Genheden","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"670158","DOI":"10.3389\/fphar.2021.670158","article-title":"The Depolarization-Evoked, Ca2+-Dependent Release of Exosomes from Mouse Cortical Nerve Endings: New Insights into Synaptic Transmission","volume":"22","author":"Olivero","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4785","DOI":"10.1111\/bph.14061","article-title":"Immuno-pharmacological characterization of group II metabotropic glutamate receptors controlling glutamate exocytosis in mouse cortex and spinal cord","volume":"174","author":"Olivero","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/0014-2999(74)90272-6","article-title":"A Simple Apparatus for Studying the Release of Neurotransmitters from Synaptosomes","volume":"25","author":"Raiteri","year":"1974","journal-title":"Eur. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1111\/bph.13442","article-title":"Presynaptic, release-regulating mGlu2 -preferring and mGlu3 -preferring autoreceptors in CNS: Pharmacological profiles and functional roles in demyelinating disease","volume":"173","author":"Merega","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1023\/A:1007648229795","article-title":"Synaptosomes still viable after 25 years of superfusion","volume":"25","author":"Raiteri","year":"2000","journal-title":"Neurochem. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.1007\/s12035-019-1511-8","article-title":"Immuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases","volume":"56","author":"Olivero","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Qu, L., Zhou, Q.T., Wu, D., and Zhao, S.W. (2019). Crystal structures of the alpha2A adrenergic receptor in complex with an antagonist RSC. Released Protein Data Bank.","DOI":"10.2210\/pdb6kux\/pdb"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/jcc.21666","article-title":"Assessing the performance of the molecular mechanics\/Poisson Boltzmann surface area and molecular mechanics\/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking","volume":"32","author":"Hou","year":"2011","journal-title":"J. Comp. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models","volume":"33","author":"Kollman","year":"2000","journal-title":"Acc. Chem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9478","DOI":"10.1021\/acs.chemrev.9b00055","article-title":"End-Point Binding Free Energy Calculation with MM\/PBSA and MM\/GBSA: Strategies and Applications in Drug Design","volume":"119","author":"Wang","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Pittaluga, A. (2019). Acute Functional Adaptations in Isolated Presynaptic Terminals Unveil Synaptosomal Learning and Memory. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153641"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1111\/j.1476-5381.1992.tb13421.x","article-title":"Subclassification of release-regulating alpha 2-autoreceptors in human brain cortex","volume":"107","author":"Raiteri","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/BF00504997","article-title":"Noradrenaline uptake inhibitors do not reduce the presynaptic action of clonidine on 3H-noradrenaline release in superfused synaptosomes","volume":"327","author":"Maura","year":"1984","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/11\/1759\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:25:37Z","timestamp":1760167537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/10\/11\/1759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":64,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["antiox10111759"],"URL":"https:\/\/doi.org\/10.3390\/antiox10111759","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]}}}