Development of Thermally and Photochemically Stable Anesthetic Components

Low photo- and thermal stability of (R)-epinephrine (vasoconstrictor) in local anesthetic formulations compromises their anesthetic efficacy in field austere environments. The overall objective of this proposal (Phase I and Phase II combined) is tosynthesize potentially stable vasoconstrictors, study their stability, and prove their anesthetic efficacy. During Phase I of this contract, we developed technology and synthesized fluorinated derivatives of (R)-epinephrine and (R)-phenylephrine possessingsuperior stability compared to the standard compounds. To continue this works, we propose in Phase II to expand the list of prospective candidates, optimize the synthesis of our fluorinated chiral derivatives, perform biological assays to determine thereceptor affinities for these compounds in vitro, study toxicity and demonstrate their anesthetic efficacy. Successful candidates will be commercialized in DoD and private sector.Many third world countries do not have climate-controlled environments tosafely store pharmaceuticals. Transport and storage of anesthetic to these regions, especially in hot climates, may compromise the efficacy of the drug. Development of new anesthetic components would be of great benefit to the oral care of many civiliansin these nations, as well as military personnel deployed in austere environments.