{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:37:10Z","timestamp":1785285430099,"version":"3.55.0"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,6,20]],"date-time":"2013-06-20T00:00:00Z","timestamp":1371686400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors (ARs) are important modulators of a wide array of physiological responses. As only a few selective compounds for the three \u03b1<jats:sub>2<\/jats:sub>\u2010AR subtypes (\u03b1<jats:sub>2A<\/jats:sub>, \u03b1<jats:sub>2B<\/jats:sub> and \u03b1<jats:sub>2C<\/jats:sub>) have been available, the pharmacological profile of a new \u03b1<jats:sub>2C<\/jats:sub>\u2010selective AR antagonist ORM\u201010921 is reported. Standard <jats:italic>in vitro<\/jats:italic> receptor assays and antagonism of \u03b1<jats:sub>2<\/jats:sub>, and \u03b1<jats:sub>1<\/jats:sub>\u2010AR agonist \u2010evoked responses <jats:italic>in vivo<\/jats:italic> were used to demonstrate the \u03b1<jats:sub>2C<\/jats:sub>\u2010AR selectivity for ORM\u201010921 which was tested in established behavioural models related to schizophrenia and cognitive dysfunction with an emphasis on pharmacologically induced hypoglutamatergic state by phencyclidine or MK\u2010801. The Kb values of <jats:italic>in vitro<\/jats:italic> \u03b1<jats:sub>2C<\/jats:sub>\u2010 AR antagonism for ORM\u201010921 varied between 0.078\u20131.2\u00a0<jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content> depending on the applied method. The selectivity ratios compared to \u03b1<jats:sub>2A<\/jats:sub>\u2010AR subtype and other relevant receptors were 10\u2010100 times <jats:italic>in vitro<\/jats:italic>. The <jats:italic>in vivo<\/jats:italic> experiments supported its potent \u03b1<jats:sub>2C<\/jats:sub>\u2010antagonism combined with only a weak \u03b1<jats:sub>2A<\/jats:sub>\u2010antagonism. In the pharmacodynamic microdialysis study, ORM\u201010921 was found to increase extracellular dopamine levels in prefrontal cortex in the baseline conditions. In the behavioural tests, ORM\u201010921 displayed potent antidepressant and antipsychotic\u2010like effects in the forced swimming test and prepulse\u2010inhibition models analogously with the previously reported results with structurally different \u03b1<jats:sub>2C<\/jats:sub>\u2010selective AR antagonist JP\u20101302. Our new results also indicate that ORM\u201010921 alleviated the NMDA\u2010antagonist\u2010induced impairments in social behaviour and watermaze navigation. This study extends and further validates the concept that \u03b1<jats:sub>2C<\/jats:sub>\u2010AR is a potential therapeutic target in CNS disorders such as schizophrenia or Alzheimer's disease and suggests the potential of \u03b1<jats:sub>2C<\/jats:sub>\u2010antagonism to treat such disorders<jats:bold>.<\/jats:bold><\/jats:p>","DOI":"10.1111\/bcpt.12090","type":"journal-article","created":{"date-parts":[[2013,5,30]],"date-time":"2013-05-30T05:25:49Z","timestamp":1369891549000},"page":"239-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Pharmacological Characterisation of a Structurally Novel \u03b1<sub>2C<\/sub> \u2010Adrenoceptor Antagonist <scp>ORM<\/scp>\u201010921 and its Effects in Neuropsychiatric Models"],"prefix":"10.1111","volume":"113","author":[{"given":"Jukka","family":"Sallinen","sequence":"first","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Holappa","sequence":"additional","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Koivisto","sequence":"additional","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Kuokkanen","sequence":"additional","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Chapman","sequence":"additional","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyrki","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[{"name":"Orion Corporation Orion Pharma Research and Development Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petteri","family":"Piepponen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mijatovic","sequence":"additional","affiliation":[{"name":"Division of Pharmacology and Toxicology University of Helsinki Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Tanila","sequence":"additional","affiliation":[{"name":"Department of Neurobiology A. 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