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dc.contributor.advisorRyder, Sheila
dc.contributor.authorKhan, Denise
dc.date.accessioned2016-12-01T10:15:46Z
dc.date.available2016-12-01T10:15:46Z
dc.date.issued2009
dc.identifier.citationDenise Khan, 'The pharmacological effects of novel isosorbide-based butyrylcholinesterase inhibitors', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2009, pp 405
dc.identifier.otherTHESIS 8854
dc.identifier.urihttp://hdl.handle.net/2262/78042
dc.description.abstractThis study sought to determine the pharmacological effects of novel isosorbide-based butyrylcholinesterase inhibitors (BuChEl’s) in vitro and in vivo. The potency of the novel compounds 2-benzylcarbamate 5-nicotinate (compound 21), 2-benzylcarbamate 5-salicylate (compound 30), mono-ethyl carbamate 5-salicylate (compound 33), isosorbide-2-benzylcarbmate 5 benzoate (compound 51) and isosorbide-2- butylcarbamate 5-benzoate (compound 57) were assessed in human and mouse plasma using the Ellman assay.The most potent compounds were then profiled in vivo in a mouse model using a protocol based upon the Shirpa profile. Administration of the novel compounds did not reveal any abnormalities.In vivo toxicology studies did not reveal any signs of hepatoxicity with I mg/kg of compound 51. However, 10 mg/kg of compound 51 and 2 mg/kg of compound 30 revealed gross changes in the liver. Histological evidence confirmed hepatoxicity secondary to necrosis. Following preliminary dose-ranging studies in vivo, the pharmacodynamics of compound 51 and compound 30 were assessed in male C57BL/6 mice by various routes of administration. Administration of 1 mg/kg of compound 51 intraperitoneally (i.p.) and orally (p.o.) produced 40% and 60% inhibition of plasma BuChE respectively. This peripheral inhibition was relatively short-lived with recovery of plasma BuChE levels 30 minutes following i.p. and 1 hour following oral administration. 2 mg/kg of compound 30 i.p. produced approximately 25% inhibition of plasma BuChE 30 minutes following administration, with plasma BuChE levels recovering thereafter.
dc.format1 volume
dc.language.isoen
dc.publisherTrinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
dc.relation.isversionofhttp://stella.catalogue.tcd.ie/iii/encore/record/C__Rb14132488
dc.subjectPharmacy, Ph.D.
dc.subjectPh.D. Trinity College Dublin
dc.titleThe pharmacological effects of novel isosorbide-based butyrylcholinesterase inhibitors
dc.typethesis
dc.type.supercollectionthesis_dissertations
dc.type.supercollectionrefereed_publications
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (Ph.D.)
dc.rights.ecaccessrightsopenAccess
dc.format.extentpaginationpp 405
dc.description.noteTARA (Trinity’s Access to Research Archive) has a robust takedown policy. Please contact us if you have any concerns: rssadmin@tcd.ie


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