Paralytic shellfish poisoning (PSP) is a severe and occasionally
fatal neurological illness caused by consumption of shellfish
contaminated with potent neurotoxins. Such toxins are produced
by “red tide” dinoflagellates belonging to Alexandrium, Pyrodinium,
and Gymnodinium genera, subsequently accumulated in wild and
cultured shellfish, and finally transmitted to humans through the
food chain.1
Structurally, PSP toxins (Figure 1) are based on the parent
compound, saxitoxin (STX), which possesses some interesting
structural features, namely, a tetrahydropurine moiety with a fivemembered
ring fused at an angular position and a ketone hydrate
stabilized by two neighboring electron-withdrawing guanidinium
groups. Several derivatives of STX are formed by addition of
hydroxyl or hydroxysulfate groups at the C11 position, Nhydroxylation
at the N1 position, N-sulfation at the N21 position,
or decarbamoylation to a hydroxyl function at the C17 position.
Due to differences in charge state and substitutions on the basic
STX structure, various PSP toxins bind with different affinities to
site 1 of sodium channels, resulting in different toxicities: the
carbamoyl toxins are the most toxic and the N-sulfocarbamoyl
derivatives are the least toxic. However, the latter can be converted
into their highly toxic carbamoyl counterparts at low pH, such as
in the stomach.