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dc.contributor.advisorSylte, Ingebrigt
dc.contributor.advisorKristiansen, Kurt
dc.contributor.authorBøgwald, Isak Andreas
dc.date.accessioned2018-06-22T10:24:51Z
dc.date.available2018-06-22T10:24:51Z
dc.date.issued2016-06-01
dc.description.abstractAntidepressants are the most common treatment of depression, one of the leading causes of suicide and disability worldwide. Currently marketed antidepressants have certain limitations; they have a delayed response time, only about 1/3 of the patients respond to the first agent prescribed, and many of them produce side effects that reduce the quality of life. The need for more efficacious and faster-acting antidepressants with fewer side effects is thus apparent. Studies have shown that 5-HT receptors (5-HTRs) are involved in many of the adverse effects of antidepressants, and may be responsible for efficacy issues and the delayed onset of therapeutic action. Some novel multimodal (two or more pharmacological actions) antidepressants combine inhibition of the serotonin transporter (SERT) with agonist or antagonist activity at 5-HTRs, to counteract the activity responsible for the aforementioned problems with the present antidepressants. This study continues a previous virtual screening study, where we identified new compounds for SERT. Several of the compounds also showed affinity for one or more 5-HTRs. Although affinities are known, their ligand – 5-HTRs binding modes and their mode of action (agonist or antagonist action) for the target 5-HTRs have not been established. The aim of this study was to predict their mode of action, and to identify binding modes important for high affinity, by the use of computational methods. Homology modeling was used to construct models of 5-HT1AR, 5-HT2AR, 5-HT6R and 5-HT7R. The models were used for molecular docking and calculations of structural interaction fingerprints. Several residues important for affinity to the target receptors were identified, and preferable binding modes were determined. The mode of action of the compounds was predicted based on their preferences for agonist/antagonist-selective models, and on previous studies of agonists and antagonists showing that agonists form strong polar interactions transmembrane helix 5 (TM5). The results indicated that several of the compounds might have potential to be developed into new antidepressant drugs.en_US
dc.identifier.urihttps://hdl.handle.net/10037/12966
dc.language.isoengen_US
dc.publisherUiT Norges arktiske universiteten_US
dc.publisherUiT The Arctic University of Norwayen_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2016 The Author(s)
dc.subject.courseIDMBI-3941
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Farmakologi: 728en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Pharmacology: 728en_US
dc.titleBinding mode of novel multimodal serotonin transporter compounds in 5-hydroxytryptamine receptorsen_US
dc.typeMaster thesisen_US
dc.typeMastergradsoppgaveen_US


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