PRINCIPLES OF TOXICOLOGY

424 PROPERTIES AND EFFECTS OF NATURAL TOXINS AND VENOMS
Figure 17.6 The Eastern diamondback rattlesnake (Crotalus adamanteus) is one of the most dangerous pit vipers.
On a weight basis its venom is not nearly as powerful as cobra or coral snake venom, but it compensates for this
by injecting a much larger quantity of venom with an efficient venom delivery apparatus.
Cobra or sea snake envenomation often causes respiratory arrest before any signs of local tissue or
systemic cardiovascular damage are apparent. The major neurotoxin occurring in elapid and
hydrophiid venoms is α-neurotoxin. This is a basic polypeptide of 65–80 amino acid residues that
is crosslinked with four or five disulfide bonds. The toxin acts as a competitive antagonist of the
neurotransmitter acetylcholine (ACh) at the skeletal muscle neuromuscular junction. Unlike the
nondepolarizing muscle relaxants used in surgery, which act at the same site, α-neurotoxin binds
very tightly because its greater molecular size permits many contacts with the nicotinic receptor.
In fact, a toxin found in the Taiwanese krait (Bungarus multicinctus), alpha-bungarotoxin, binds
essentially irreversibly to the skeletal muscle nicotinic receptor, preventing ACh from interacting
with its postsynaptic receptor. As if this potent neurotoxin were not sufficient to paralyze the
skeletal muscle, this snake also makes a larger protein toxin called beta-bungarotoxin (Table 17.1),
which inhibits the release of ACh from the motor nerve terminal; these two toxins, working
together in a synergistic fashion, can reduce the probability of neuromuscular transmission to
zero. Besides the postsynaptic alpha-neurotoxic peptides, elapid venoms also generally contain
phospholipase A and a peptide called cardiotoxin, which is a cytolysin that tends to attack cardiac
myocardial cells. Cardiotoxin disrupts the bilayer structure of membrane lipids, and thereby makes
these lipids more accessible substrates for the phospholipase A.
Coral snakes are the only new-world elapids. About 50 species have been described. In the United
States there are only two species, but in central America and the northern parts of South America there
are many species. Coral snake bites are rarely as life-threatening as cobra bites because the volume of
venom injected is usually quite small. Elapid snakes lack the fangs observed in the pit vipers, and
therefore, they must resort to a more lengthy chewing method of envenomation, which is not nearly
as efficient. The major danger for elapid snake envenomation victims is respiratory arrest due to
blockade of neuromuscular transmission, and secondarily, cardiac systolic arrest due to the synergistic