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As a graduate student, I discovered a toxin, anabaseine, which a marine worm uses to paralyze its prey. More recently, in a project with Drs. Meyer and Papke, we demonstrated that this bicyclic nicotinic alkaloid, when derivatized with an aromatic aldehyde, yields a compound which selectively stimulates alpha7 nicotinic receptors in the brain and enhances cognition. DMXBA (GTS-21) also displays neuroprotective activity and is much less toxic than nicotine. Phase I clinical tests of this compound were completed recently, and its utility for treating Alzheimer’s disease and schizophrenia will be assessed in the near future. Unlike the high affinity nicotinic receptors which drastically decrease in number as Alzheimer’s disease progresses, alpha 7 receptors are not greatly affected and therefore can continue to serve as a CNS drug target. We recently demonstrated that the primary metabolites of GTS-21 are even more potent alpha7 agonists than the parent compound and can serve as models for design of even more optimized drug candidates.
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Zootaxano. 4 (2023): 596-599
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