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The anticonvulsant actions of novel ’broad-spectrum’ Ca2+ channel blockers and low affinity, uncompetitive NMDA receptor antagonists

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dc.contributor.author Thurgur, Claire Helen
dc.date.accessioned 2009-03-07
dc.date.available 2009-03-07
dc.date.copyright 1996 en
dc.date.issued 2009-03-07
dc.identifier.uri http://hdl.handle.net/2429/5731
dc.description.abstract Epilepsy is a prominent neurological disorder. Presently available anticonvulsant drugs however fail to alleviate seizures in approximately 25% of individuals, and are often accompanied by serious side effects. More efficacious and less toxic agents are required. In this study, the effects of a range of structurally dissimilar a site ligands were examined against evoked and spontaneous epileptiform activity induced in rat hippocampal slices by perfusion with Mg2+-free medium. Extracellular recordings were made in the CA1 hippocampal region of epileptiform activity evoked by stimulation of the Schaffer collateral (SC) pathway, and of spontaneous epileptiform activity originating from the CA3 hippocampal region. Evoked and spontaneous epileptiform activity was inhibited by all compounds tested with the rank order (IC5 0 values against evoked epileptiform activity in uM): dextrorphan (2) > ifenprodil (6) > dextromethorphan (10) > l,3-di(2-tolyl)guanidine (15) > loperamide (28) > carbetapentane (38) > caramiphen (46) > opipramol (52). Ifenprodil, loperamide, caramiphen and dextrorphan were also examined for their effects on the input/output (I/O) functions along the SC pathway and on the paired pulse facilitation (PPF) ratio. An effect was observed only in the presence of caramiphen, which showed a decrease in the synaptic transmission I/O function and reduced markedly the PPF ratio. The (micromolar) concentrations required for the anticonvulsant activity of the CT ligands tested suggests that their anticonvulsant actions are not mediated by high affinity (nanomolar) binding to rj binding sites, but rather to blockade of high voltage activated Ca2 + channels and/or NMD A receptors, actions which occur at micromolar concentrations. en
dc.format.extent 6538296 bytes
dc.format.mimetype application/pdf
dc.language.iso eng en
dc.relation.ispartofseries UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/]
dc.title The anticonvulsant actions of novel ’broad-spectrum’ Ca2+ channel blockers and low affinity, uncompetitive NMDA receptor antagonists en
dc.type Electronic Thesis or Dissertation
dc.degree.name Master of Science - MSc en
dc.degree.discipline Anatomy en
dc.degree.grantor University of British Columbia
dc.date.graduation 1997-05 en
dc.degree.campus UBCV en

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