{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:40:21Z","timestamp":1790142021270,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct <jats:italic>in vitro<\/jats:italic> pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We evaluated quetiapine and norquetiapine, using <jats:italic>in vitro<\/jats:italic> binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the <jats:italic>in vitro<\/jats:italic> pharmacological properties translate into <jats:italic>in vivo<\/jats:italic> activity, we used preclinical animal models with translational relevance to established antidepressant\u2010like and anxiolytic\u2010like drug action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In <jats:italic>in vivo<\/jats:italic> receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5\u2010HT<jats:sub>1A<\/jats:sub> receptors, and the anxiolytic\u2010like activity of norquetiapine in rat punished responding was blocked by the 5\u2010HT<jats:sub>1A<\/jats:sub> antagonist, WAY100635.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Quetiapine and norquetiapine have multiple <jats:italic>in vitro<\/jats:italic> pharmacological actions, and results from preclinical studies suggest that activity at NET and 5\u2010HT<jats:sub>1A<\/jats:sub> receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13346","type":"journal-article","created":{"date-parts":[[2015,10,5]],"date-time":"2015-10-05T22:00:45Z","timestamp":1444082445000},"page":"155-166","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Quetiapine and its 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