text: NSTX blocks the extracellular portion, the outer vestibule, of some voltage gated sodium channels in a very powerful and reversible manner, without affection of other ion channels.
  "Voltage-gated", also called "voltage-sensitive" and "voltage-dependent" sodium channel also known as "VGSCs" or "Nav channel" are crucial elements of normal physiology in a variety of animals, including flies, leeches, squid and jellyfish, as well as mammalian and non-mammalian vertebrates. This large integral membrane protein plays an essential role in the initiation and propagation of action potentials in neurons, myocytes and other excitable cells.
  Nav channels form the basis for electrical excitability in animals. Nav channels evolved from Ca channels and were present in the common ancestor of choanoflagellates and animals, although this channel was likely permeable to both Na and Ca. Thus, like many other neuronal channels and receptors, Nav channels predated neurons. Invertebrates possess two Nav channels (Nav1 and Nav2), whereas vertebrate Nav channels are of the Nav1 family.
  Sodium-channel proteins in the mammalian brain are composed of an association that include one alpha subunit and one or more auxiliary beta subunits. Nine types of alpha subunits have been described (Na1.1 to Na1.9), and a tenth related isoform (Na) may also play some role as a Nav channel. Based in this information, ten Nav classes can be described: Na1.1 to Na1.9, and Na.
  Former five, but more recently, six neurotoxin receptor sites have been recognized between the seven receptor site located in the vertebrate sodium channel receptor alpha subunit:
  * Site 1 binds the sodium channel blockers tetrodotoxin and saxitoxin.
  * Site 2 binds lipid-soluble sodium channel activators such as veratridine.
  * Site 3 binds alpha-scorpion and sea anemone toxins, which slow sodium channel inactivation.
  * Site 4 binds beta-scorpion toxins, which affect sodium channel activation.
  * Site 5 binds the polyether ladder brevetoxins and ciguatoxin.
  * Site 6 binds delta-conotoxin.
  * Local anesthetic receptor site binds local anesthetics, antiarrhythmic drugs and antiepileptic drugs
  NSTX and other site 1 blockers have high affinity (very low dissociation constant) and high specificity for Nav channels. The action of NSTX produces minimal effect on cardiac Nav, where it exhibits about 20–60 fold lesser affinity than in Nav channels from rat skeletal muscle and rat brain. Most data emphasize the role of "STX resistant" Na channel 1.5 in human heart.
  Toxins such as neosaxitoxin and tetrodotoxin have less affinity for most cardiac Nav channels than for most Nav channels in nerve tissue. Moreover, NSTX is so active on nerve Nav channel than is roughly a million-fold more potent than lidocaine.