Bearsden Bio Inc. has developed novel compounds that selectively regulate glutamate receptor subtypes. In Phase I we synthesized a large number of AMPA receptor allosteric antagonists and tested them for inhibition of APA and kainate induced calcium influx into cortical cells. We were able to group the over 50 compounds into categories and determine their structure/activity profile. We also tested the activity of some promising compounds against MES induced seizures and compared it to their sedative effect on the rotarod. Our structure activity program from Phase I produced ligands that exhibit good affinity for AMPA receptors and promising separation between the desired anticonvulsant response and the major side effect, the drop in performance on the rotarod. We continued to synthesize new analogs to better understand the structure activity relation of the compounds and we have, to date, identified several more compounds with promising in vitro activity. We are seeking Phase II funding to better understand the mechanism of action of these novel AMPA antagonists including their subtype specificity and efficacy animal models of epilepsy to determine the best compound for further development we will select an allosteric AMPA antagonist as lead candidate for the treatment of epilepsy. The preclinical studies about Phase II will include pharmacokinetics, metabolism and toxicity. At the same time we will be preparing alternative candidates for use as back-ups in the event our lead should not have the requisite properties of a clinical candidate for the treatment of epilepsy.
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