dc.contributor.advisor | Ryder, Sheila | |
dc.contributor.author | Khan, Denise | |
dc.date.accessioned | 2016-12-01T10:15:46Z | |
dc.date.available | 2016-12-01T10:15:46Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Denise 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.other | THESIS 8854 | |
dc.identifier.uri | http://hdl.handle.net/2262/78042 | |
dc.description.abstract | This 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.format | 1 volume | |
dc.language.iso | en | |
dc.publisher | Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences | |
dc.relation.isversionof | http://stella.catalogue.tcd.ie/iii/encore/record/C__Rb14132488 | |
dc.subject | Pharmacy, Ph.D. | |
dc.subject | Ph.D. Trinity College Dublin | |
dc.title | The pharmacological effects of novel isosorbide-based butyrylcholinesterase inhibitors | |
dc.type | thesis | |
dc.type.supercollection | thesis_dissertations | |
dc.type.supercollection | refereed_publications | |
dc.type.qualificationlevel | Doctoral | |
dc.type.qualificationname | Doctor of Philosophy (Ph.D.) | |
dc.rights.ecaccessrights | openAccess | |
dc.format.extentpagination | pp 405 | |
dc.description.note | TARA (Trinity’s Access to Research Archive) has a robust takedown policy. Please contact us if you have any concerns: rssadmin@tcd.ie | |