Previous studies with ADD234037 (R-2-Acetamido-N-Benzyl-3-Methoxypropionamide) a functionalized amino acid derivative, have demonstrated its anticonvulsant and neuroprotective properties. This compound is currently being evaluated in Phase II clinical studies for its utility in the treatment of epilepsy and neuropathic pain. Preliminary studies have demonstrated similar anticonvulsant activities with close analogs of ADD234037. Research to evaluate each of these compounds will progress in a stepwise fashion. Further studies will be undertaken to determine receptor affinities for each compound. Based upon these results, selected candidates will be evaluated for neuroprotective activity in in vitro and in viva models. Safety evaluation will be conducted on the most interesting compound in the series. The lead compound at this final stage will be tested in an in viva animal model of stroke. Several concerns were raised during the discussion. For example, how does the neuronal damage protection observed with harkoseride (under conditions of perforate path stimulation in status epilepticus) relate to neuroprotection in ischemia? Also, a three-vessel occlusion model of ischemia would yield better, more reproducible lesions, which would be a more reliable model for ischemia screening. The proposed model gives much more lesion variability, which would make it much more statistically difficult to detect a significant improvement with the selected compounds. A three-vessel occlusion model of ischemic would give better, more reproducible lesions, which would be a more reliable model for ischemia screening. Also, how does the neuronal damage protect with harkoseride (via perforate path stimulation in status epileptics) related to neuroprotection in ischemia.
Thesaurus Terms: aminoacid analog, anticonvulsant, drug design /synthesis /production, drug screening /evaluation, neuroprotectant, stroke therapy cerebral ischemia /hypoxia, receptor binding, stroke gerbil /jird, laboratory mouse, laboratory rat, tissue /cell culture
