Oral General Anesthetics and Metabolically Resistant Anticonvulsants

Executive Summary
A researcher at the University of Virginia has discovered a group of novel compounds that have activity as anesthetics, anticonvulsants and neuroprotective agents. These compounds are unique in that they have been modified to prevent the formation of a common toxic metabolite.

Background
Themisone has been widely utilized as an anticonvulsant since its discovery in the early 1950s. Despite the drug’s substantial neuroprotective properties, themisone is known to suffer from the production of potentially harmful metabolites.  

About the Invention
Milton L. Brown, M.D., Ph.D., discovered a novel, potent class of themisone analogues that prevent formation of toxic metabolites and have shown enhanced potency and safety through biological testing. Synthesis of these analogs was achieved in a straightforward manner providing the desired product materials in good yield. Biological evaluation in animal models of anticonvulsant activity was conducted through NIH screening, in which maximal electrode shock was utilized to determine anticonvulsant activity and rotorod motor skills were used to evaluate toxicity. During this screening process, numerous compounds were found to provide significant neuroprotection with reduced levels of toxicity. Additionally, evaluation for minimal alveolar concentration (MAC) has proven these compounds to be potent general anesthetics. U.S. patent 7,414,078 has been issued on this technology.

Advantages
The invention

• Is based on a well characterized parent compound
• Does not produce the toxic metabolite, 2-phenyl-acrylamide
• Can serve as a general anesthetic, an anticonvulsant and a neuroprotective agent
• Has demonstrated effectiveness in in vivo models