dc.contributor.advisor | Muma, Nancy A | |
dc.contributor.author | Ladd, Amanda | |
dc.date.accessioned | 2018-03-09T22:35:29Z | |
dc.date.available | 2018-03-09T22:35:29Z | |
dc.date.issued | 2017-05-31 | |
dc.date.submitted | 2017 | |
dc.identifier.other | http://dissertations.umi.com/ku:15102 | |
dc.identifier.uri | http://hdl.handle.net/1808/26155 | |
dc.description.abstract | Atypical antipsychotics are used to treat schizophrenia and although atypical antipsychotics helped improve the management of positive symptoms, many patients are still suffering from negative and cognitive symptoms and side effects. Serotonin-2A receptors have been implicated in the mechanism of action of atypical antipsychotics. Atypical antipsychotics such as olanzapine and clozapine are antagonists of 5-HT2A/Gαq/11 pathway, but activate the 5-HT2A/JAK2/STAT3 pathway. Studying the functional selectivity of atypical antipsychotics at the 5-HT2A receptor may lead to a better understanding of the role that 5-HT2A receptors play in the therapeutic effect of atypical antipsychotics. This dissertation investigates five analogs of olanzapine and the 5-HT2A receptor antagonist, ketanserin, for functional selectivity at the 5-HT2A receptor. A calcium mobilization assay was used to investigate the 5-HT2A/Gαq/11 pathway and immunoblotting was used to investigate the 5-HT2A/JAK2/STAT3. We identified three analogs that induced calcium mobilization and two analogs that prevented 5-HT2A receptor agonist induced calcium mobilization. We also found that four analogs induced phosphorylation of JAK2 and one analog that prevented 5-HT2A receptor agonist induced phosphorylation of JAK2. In the future, functionally selective analogs can be used to study the 5-HT2A/Gαq/11 and 5-HT2A/JAK2/STAT3 pathways separately in order to gain a better understanding of the role each individual pathway plays in the therapeutic effect of atypical antipsychotics. | |
dc.format.extent | 49 pages | |
dc.language.iso | en | |
dc.publisher | University of Kansas | |
dc.rights | Copyright held by the author. | |
dc.subject | Pharmacology | |
dc.subject | atypical antipsychotics | |
dc.subject | serotonin-2A receptors | |
dc.title | IDENTIFYING FUNCTIONALLY SELECTIVE LIGANDS FOR THE SEROTONIN-2A RECEPTOR | |
dc.type | Thesis | |
dc.contributor.cmtemember | Shi, Honglian | |
dc.contributor.cmtemember | Zhao, Liqin | |
dc.thesis.degreeDiscipline | Pharmacology & Toxicology | |
dc.thesis.degreeLevel | M.S. | |
dc.identifier.orcid | | |
dc.rights.accessrights | openAccess | |