{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/11275"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/11275","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Design, Synthesis, and Pharmacological Characterization of Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) Positive Allosteric Modulators","abstract":"A decreased signaling capacity at the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) regulates neurobehavioral processes that may underlie chronic health issues such as impulsivity disorders, drug addiction, depression, schizophrenia, and obesity. Therefore, restoration of the diminished signaling capacity through 5-HT2CR activation has therapeutic potential. A series of new molecules based on the 4-alkylpiperidine-2- carboxamide scaffold and oleamide were designed, synthesized, and pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors (e.g., spontaneous motor activity and drug discrimination) in rats. Two predicted allosteric sites were identified by molecular docking to a 5-HT2CR homology model. Taken together, these data represent the only combination of in vitro and in vivo evidence of a synthetic small molecule acting as a 5-HT2CR PAM providing a proof of concept that allosteric modulation of 5-HT2CR is a viable strategy toward the discovery of novel neurotherapeutics.","abstract_html":"A decreased signaling capacity at the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) regulates neurobehavioral processes that may underlie chronic health issues such as impulsivity disorders, drug addiction, depression, schizophrenia, and obesity. Therefore, restoration of the diminished signaling capacity through 5-HT2CR activation has therapeutic potential. A series of new molecules based on the 4-alkylpiperidine-2- carboxamide scaffold and oleamide were designed, synthesized, and pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors (e.g., spontaneous motor activity and drug discrimination) in rats. Two predicted allosteric sites were identified by molecular docking to a 5-HT2CR homology model. Taken together, these data represent the only combination of in vitro and in vivo evidence of a synthetic small molecule acting as a 5-HT2CR PAM providing a proof of concept that allosteric modulation of 5-HT2CR is a viable strategy toward the discovery of novel neurotherapeutics.","abstract_has_math":false,"creators":["Wild, Christopher Timothy"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Pharmacology and Toxicology (Doctoral)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:50:56Z","subjects":["serotonin, positive allosteric modulator"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/11275","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Wild, Christopher Timothy"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2021-04-21T15:48:24Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Pharmacology and Toxicology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["serotonin, positive allosteric modulator"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/11275"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A decreased signaling capacity at the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) regulates neurobehavioral processes that may underlie chronic health issues such as impulsivity disorders, drug addiction, depression, schizophrenia, and obesity. Therefore, restoration of the diminished signaling capacity through 5-HT2CR activation has therapeutic potential. A series of new molecules based on the 4-alkylpiperidine-2- carboxamide scaffold and oleamide were designed, synthesized, and pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors (e.g., spontaneous motor activity and drug discrimination) in rats. Two predicted allosteric sites were identified by molecular docking to a 5-HT2CR homology model. Taken together, these data represent the only combination of in vitro and in vivo evidence of a synthetic small molecule acting as a 5-HT2CR PAM providing a proof of concept that allosteric modulation of 5-HT2CR is a viable strategy toward the discovery of novel neurotherapeutics."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Design, Synthesis, and Pharmacological Characterization of Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) Positive Allosteric Modulators"]}]}],"canonical_facts":{"dc:creator":["Wild, Christopher Timothy"],"dc:date.accessioned":["2021-04-21T15:48:24Z"],"dc:description.abstract":["A decreased signaling capacity at the serotonin (5-HT) 5-HT2C receptor (5-HT2CR) regulates neurobehavioral processes that may underlie chronic health issues such as impulsivity disorders, drug addiction, depression, schizophrenia, and obesity. Therefore, restoration of the diminished signaling capacity through 5-HT2CR activation has therapeutic potential. A series of new molecules based on the 4-alkylpiperidine-2- carboxamide scaffold and oleamide were designed, synthesized, and pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors (e.g., spontaneous motor activity and drug discrimination) in rats. Two predicted allosteric sites were identified by molecular docking to a 5-HT2CR homology model. Taken together, these data represent the only combination of in vitro and in vivo evidence of a synthetic small molecule acting as a 5-HT2CR PAM providing a proof of concept that allosteric modulation of 5-HT2CR is a viable strategy toward the discovery of novel neurotherapeutics."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152.3/11275"],"dc:subject":["serotonin, positive allosteric modulator"],"dc:title":["Design, Synthesis, and Pharmacological Characterization of Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) Positive Allosteric Modulators"],"dc:type":["Thesis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Pharmacology and Toxicology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:50:56Z"}