{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:25:05Z","timestamp":1793316305178,"version":"4.5.0"},"reference-count":54,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T00:00:00Z","timestamp":1732838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:p>\n                    Understanding neuromodulatory effects of serotonin 2A receptor (5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R) agonists with diverse pharmacological profiles is relevant to advancing psychedelic-related drug applications. We performed simultaneous positron emission tomography (PET) and pharmacological magnetic resonance imaging (phMRI) in anesthetized nonhuman primates (NHP; N\u2009=\u20093) to examine partial agonists with varying 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R affinities and selectivity profiles: psilocybin (30, 60, and 90\u2009\u00b5g\/kg), lisuride (5\u2009\u00b5g\/kg), and 25CN-NBOH (15\u2009\u00b5g\/kg). Receptor occupancy was assessed with [\n                    <jats:sup>11<\/jats:sup>\n                    C]MDL-100907 PET, and cerebral blood volume (CBV) changes were measured with phMRI. Mixed partial agonists psilocybin and lisuride evoked biphasic CBV responses, whereas the selective 25CN-NBOH produced monophasic CBV increases. Cortical occupancy for psilocybin plateaued at 60\u2009\u00b5g\/kg (32%), whereas a lower dose of lisuride (5\u2009\u00b5g\/kg) resulted in similar occupancy (31%). Administration of 25CN-NBOH resulted in lower occupancy (7%) but larger changes in CBV compared to psilocybin and lisuride. The associations between CBV and 5-HT\n                    <jats:sub>2A<\/jats:sub>\n                    R occupancy appear linear for lisuride and 25CN-NBOH, but not for psilocybin. We speculate that the temporal and spatial differences in hemodynamic responses of the three agonists could stem from mixed affinity profiles. This work provides an understanding of pharmacological impacts of mixed serotonergic agonists being pursued as therapeutics for psychiatric conditions, offering valuable insights for future drug applications and development strategies.\n                  <\/jats:p>","DOI":"10.1177\/0271678x241302937","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T03:39:37Z","timestamp":1732851577000},"page":"908-919","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Neurochemical characterization of 5-HT\n                    <sub>2A<\/sub>\n                    R partial agonists with simultaneous PET-MRI"],"prefix":"10.1177","volume":"45","author":[{"given":"Frederick A","family":"Bagdasarian","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Larsen","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital"},{"name":"Department of Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Ping","family":"Deng","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick M","family":"Fisher","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital"},{"name":"Department of Drug Design and Pharmacology, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-5396","authenticated-orcid":false,"given":"Joseph B","family":"Mandeville","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-8615","authenticated-orcid":false,"given":"Christin Y","family":"Sander","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-8489","authenticated-orcid":false,"given":"Hsiao-Ying","family":"Wey","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"},{"name":"Center for the Neuroscience of Psychedelics, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5564-7627","authenticated-orcid":false,"given":"Hanne D","family":"Hansen","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital"},{"name":"Copenhagen University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyaa018"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19010035"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2017_478"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04085.x"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.03.075"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1971-17.2017"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2015.02.009"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(01)00623-2"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.117.239905"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbs117"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518377113"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25335"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20265"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.1910390415"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1109\/42.668698"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.10062"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/cbmr.1996.0014"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.2002.1132"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fninf.2012.00027"},{"key":"e_1_3_5_21_2","unstructured":"Avants BB Tustison N Johnson H. 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