{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:31:19Z","timestamp":1777858279546,"version":"3.51.4"},"reference-count":85,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1104184, APP1044624, APP1125937"],"award-info":[{"award-number":["APP1104184, APP1044624, APP1125937"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Olanzapine is one of the most commonly used antipsychotic drugs; however, its metabolic disorders are the main obstacle in the clinic. Olanzapine is a potent antagonist of the M3 acetylcholine muscarinic receptor (M3R), while the downregulated hepatic M3R-AMPK\u03b1 signalling pathway is involved in metabolic disorders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim:<\/jats:title>\n                    <jats:p>This study investigated the effects of chronic co-treatment with cevimeline (an agonist of M3Rs) in attenuating olanzapine-induced metabolic disorders and the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Forty-eight adult female Sprague-Dawley rats were treated orally with olanzapine (2 mg\/kg, 3 times\/day (t.i.d.)) and\/or cevimeline (9 mg\/kg, t.i.d.), or control (vehicle) for 9 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Cevimeline co-treatment significantly attenuated olanzapine-induced body weight gain and glucolipid metabolic disorders. Importantly, cevimeline co-treatment attenuated olanzapine-induced upregulation of M3Rs, while the co-treatment improved olanzapine-induced downregulation of AMPK\u03b1 in the liver. Cevimeline co-treatment attenuated olanzapine-induced dyslipidaemia by modulating the hepatic M3R-AMPK\u03b1 downstream pathways. Cevimeline co-treatment also improved lower activated AKT-GSK3\u03b2 signalling to reverse impairment of glucose metabolism and insulin resistance caused by chronic olanzapine treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>These results not only support the important role of M3R antagonism and its related AMPK\u03b1 and downstream pathways in antipsychotic-induced metabolic disorders but also indicate that these pathways might be promising targets for pharmacological intervention to control these side effects caused by antipsychotic therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811211050549","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T09:32:41Z","timestamp":1635154361000},"page":"202-213","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cevimeline co-treatment attenuates olanzapine-induced metabolic disorders via modulating hepatic M3 muscarinic receptor: AMPK\u03b1 signalling pathway in female rats"],"prefix":"10.1177","volume":"36","author":[{"given":"Mei","family":"Han","sequence":"first","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia"},{"name":"School of Medicine and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamei","family":"Lian","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia"},{"name":"School of Medicine and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueqing","family":"Su","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia"},{"name":"School of Medicine and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia"},{"name":"Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-5741","authenticated-orcid":false,"given":"Chao","family":"Deng","sequence":"additional","affiliation":[{"name":"Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia"},{"name":"School of Medicine and Molecular Horizons, University of Wollongong, Wollongong, NSW, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"bibr1-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(74)90556-7"},{"key":"bibr2-02698811211050549","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.18.2.245"},{"key":"bibr3-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1002\/1099-081X(199911)20:8<369::AID-BDD200>3.0.CO;2-6"},{"key":"bibr4-02698811211050549","first-page":"81","volume":"52","author":"Arisawa H","year":"2002","journal-title":"Arzneimittelforschung"},{"key":"bibr5-02698811211050549","first-page":"225","volume":"52","author":"Arisawa H","year":"2002","journal-title":"Arzneimittelforschung"},{"key":"bibr6-02698811211050549","first-page":"14","volume":"52","author":"Arisawa H","year":"2002","journal-title":"Arzneimittelforschung"},{"key":"bibr7-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044813"},{"key":"bibr8-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1060383"},{"key":"bibr9-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-269043"},{"key":"bibr10-02698811211050549","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00643"},{"key":"bibr11-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.04.003"},{"key":"bibr12-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-2224-4"},{"key":"bibr13-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.05.004"},{"key":"bibr14-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-010-9247-4"},{"key":"bibr15-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2013.05.006"},{"key":"bibr16-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6468(05)43004-0"},{"key":"bibr17-02698811211050549","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13311"},{"key":"bibr18-02698811211050549","unstructured":"FDA (2001) Drug Approval Package > Evoxac (cevimeline HCl) NDA #20-989: Evoxac Pharmacological Review (Administration Tusfad Ed). 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