Angew Chem Int Ed Engl. 2014 Jun 2;53(23):5760-84. doi: 10.1002/anie.201308235. Epub 2014 Apr 25.


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 (Na(V)s), the obligatory proteins responsible for the initiation and propagation of action potentials. In the annals of ion channel research, the identification and characterization of Na(V)s 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 Na(V) structure and function.

Keywords: chemical probes; chemical synthesis; guanidinium toxin; neurobiology; sodium ion channel.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Biological Products / chemistry*
  • Saxitoxin / chemical synthesis*
  • Saxitoxin / chemistry*
  • Sodium Channels / drug effects*


  • Biological Products
  • Sodium Channels
  • Saxitoxin