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      <jats:p>\n                    The dopamine D\n                    <jats:sub>2<\/jats:sub>\n                    -receptor antagonist prochlorperazine is approved clinically as both an antipsychotic and an antiemetic. Classical antipsychotics like prochlorperazine have been shown to treat the positive symptoms of schizophrenia at occupancies higher than 60% with extrapyramidal symptoms occurring at occupancies over 80%. As an antiemetic, this drug is known to carry a high risk of akathisia and some risk for more severe extrapyramidal symptoms, but the relationship between dosage and D\n                    <jats:sub>2<\/jats:sub>\n                    receptor occupancies has not been reported. The functional consequences of D\n                    <jats:sub>2<\/jats:sub>\n                    receptor binding at different occupancy levels also remain unexplored in human subjects. In this study, we performed simultaneous PET and MRI to measure receptor occupancy by competition with [\n                    <jats:sup>11<\/jats:sup>\n                    C]raclopride and to assess the concurrent functional hemodynamic response versus prochlorperazine dosage. Additional studies in non-human primates (NHP) were performed for comparison and dose flexibility. In human subjects, the effective dose to achieve 50% occupancy was 1.2\u2009mg\/100-kg, indicating that a clinical dose of 10\u2009mg will achieve occupancies greater than 80% in virtually all subjects. In both human subjects and NHP, functional MRI responses showed a rapidly escalating response at occupancies larger than about 60%, a response consistent with autoreceptor-mediated dopamine release. These results provide a functional correlate for the lower edge of the antipsychotic therapeutic occupancy window and confirm that D\n                    <jats:sub>2<\/jats:sub>\n                    receptor antagonism is ineffective at attenuating post-synaptic function at low occupancies.\n                  <\/jats:p>","DOI":"10.1038\/s41386-026-02557-1","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:01:56Z","timestamp":1789729316000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Robust changes in brain function require high D2 receptor occupancy by prochlorperazine: an imaging correlate for the antipsychotic therapeutic window"],"prefix":"10.1038","author":[{"given":"Joseph B.","family":"Mandeville","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-5519","authenticated-orcid":false,"given":"Tracy","family":"Barbour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8826-5171","authenticated-orcid":false,"given":"Qikai","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-8965","authenticated-orcid":false,"given":"Hong Ping","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daphne","family":"Holt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6003-8615","authenticated-orcid":false,"given":"Christin Y.","family":"Sander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"2557_CR1","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1053\/ajem.2000.9283","volume":"18","author":"JC Olsen","year":"2000","unstructured":"Olsen JC, Keng JA, Clark JA. 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