(adapted from applicant's abstract) The proposal focuses on the design and synthesis of prodrugs of the NMDA antagonist dexanabinol (HU 211). This compound demonstrates efficacy as an antiischemic agent but may have limited therapeutic potential due to its low water solubility. The objective of the proposal is therefore to derivatize the parent compound with various esters of amino acids containing quaternary or tertiary amines and evaluate them for water and blood stability. Promising candidates will be evaluated for toxicity. Phase II studies will further develop and evaluate prodrug candidates as potential treatment for brain injury.
Thesaurus Terms:NMDA receptor, drug design /synthesis /production, inhibitor /antagonist, prodrug, water solubility cannabinoid, chemical stability, cyclodextrin, drug screening /evaluation, neuroprotectant chemical synthesis, chromatography, human tissue, laboratory ratNational Institute of Neurological Disorders and Stroke (NINDS)
