{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:54:25Z","timestamp":1792011265921,"version":"4.4.0"},"reference-count":135,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Schizophrenia remains a sizable socio\u2010economic burden that continues to be treated with therapeutics based on 70\u2010year old science. All currently approved therapeutics primarily target the dopamine D\n                      <jats:sub>2<\/jats:sub>\n                      receptor to achieve their efficacy. Whilst dopaminergic dysregulation is a key feature in this disorder, the targeting of dopaminergic machinery has yielded limited efficacy and an appreciable side effect burden. Over the recent decades, numerous drugs that engage non\u2010dopaminergic G protein\u2010coupled receptors (GPCRs) have yielded a promise of efficacy without the deleterious side effect profile, yet none have successfully completed clinical studies and progressed to the market. More recently, there has been increased attention around non\u2010dopaminergic GPCR\u2010targeting drugs, which demonstrated efficacy in some schizophrenia symptom domains. This provides renewed hope that effective schizophrenia treatment may lie outside of the dopaminergic space. Despite the potential for muscarinic receptor\u2010 (and other well\u2010characterised GPCR families) targeting drugs to treat schizophrenia, they are often plagued with complications such as lack of receptor subtype selectivity and peripheral on\u2010target side effects. Orphan GPCR studies have opened a new avenue of exploration with many demonstrating schizophrenia\u2010relevant mechanisms and a favourable expression profile, thus offering potential for novel drug development. This review discusses centrally expressed orphan GPCRs: GPR3, GPR6, GPR12, GPR52, GPR85, GPR88 and GPR139 and their relationship to schizophrenia. We review their expression, signalling mechanisms and cellular function, in conjunction with small molecule development and structural insights. We seek to provide a snapshot of the growing evidence and development potential of new classes of schizophrenia therapeutics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LINKED ARTICLES<\/jats:title>\n                    <jats:p>\n                      This article is part of a themed issue Therapeutic Targeting of G Protein\u2010Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.14\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v181.14\/issuetoc<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.16221","type":"journal-article","created":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T03:33:29Z","timestamp":1692675209000},"page":"2095-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular insights into orphan G protein\u2010coupled receptors relevant to schizophrenia"],"prefix":"10.1111","volume":"181","author":[{"given":"Yao","family":"Lu","sequence":"first","affiliation":[{"name":"Drug Discovery Biology and Neuroscience &amp; Mental Health Therapeutic Program Area, Monash Institute of Pharmaceutical 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