Saxitoxin

The paralytic agent (+)‐saxitoxin (STX), most commonly associated with oceanic red tides and shellfish poisoning, is a potent inhibitor of electrical conduction in cells. Its nefarious effects result from inhibition of voltage‐gated sodium channels (NaVs), the obligatory proteins responsible for the initiation and propagation of action potentials. In the annals of ion channel research, the identification and characterization of NaVs trace to the availability of STX and an allied guanidinium derivative, tetrodotoxin. The mystique of STX is expressed in both its function and form, as this uniquely compact dication boasts more heteroatoms than carbon centers. This Review highlights both the chemistry and chemical biology of this fascinating natural product, and offers a perspective as to how molecular design and synthesis may be used to explore NaV structure and function. …︁ and the waters that were in the river were turned to blood. And the fish that were in the river died (Exodus 7:20‐21). Its pharmacological effects having been documented since antiquity, saxitoxin holds a venerable place in the annals of natural product science. An account of both the chemistry and chemical biology of this most fascinating natural product is presented.