MAP Technical Reports Series No. 106 UNEP

- 118 -
7.2.1.8 Human intoxication: clinical toxicology
PSP causes a widespread inhibition of impulse-generation in peripheral nerves and
skeletal muscles, by blocking the sodium channel, which may result in respiratory paralysis
leading to death. Saxitoxin is one of the most lethal non-protein toxins known for man (fatal dose
1-2 mg) and approaches botulinum toxin in its lethal effects (Viviani, 1981; Steidinger and Baden,
1984; WHO, 1984). The symptoms of PSP usually appear in man in 30 min following the
consumption of toxic bivalve molluscs: paraesthesia affecting the mouth, lips, tongue, and finger
tips, profound muscular asthenia, inability to maintain an upright posture, ataxic gait, loss of
balance. Other symptoms rapidly develop, including lightheadedness, disequilibrium,
incoordination, weakness, hyperreflexia, incoherence, dysarthria, sialorrhea, dysphagia, thirst,
diarrhoea, abdominal pain, nausea, vomiting, nystagmus, dysmetria, headache, diaphoresis,
loss of vision, a sensation of loose teeth, chest pain, and tachycardia (Auerbach, 1988). The
gastro-intestinal symptoms in PSP due to Alexandrium, such as nausea, vomiting, diarrhoea
and abdominal pain are less common or do not appear at all. Unless there is a period of anoxia,
the victim will often remain awake and alert, although paralyzed. Up to 25% of victims expire
from unsupported respiratory arrest within the first 12 hr. In milder cases, alcohol ingestion
appears to increase toxicity (Acres and Gray, 1978). In the most severe forms, the clinical
setting is dominated by a progressive muscular paralysis beginning from the legs, and this
paralysis prevents standing and results in death due to respiratory paralysis. Consciousness
is rarely compromised. In lethal cases the evolution is very fast and the death occurs within 8
hr on an average, due to respiratory or cardiocirculatory deficiencies. The prognosis is
favourable in cases of survival in the first 12-24 hr (Auerbach, 1988). The mortality index is equal
to about 8-10% in the paralytic syndrome due to molluscs (Bagnis et al., 1970; WHO, 1984).
7.2.1.9 Mechanism of action
Ion channels in plasma membranes are primary targets of marine toxins. These
channels are important regulators of a cell's physiology, and many of the pathophysiological
effects of toxins arise from actions on ion channels. The voltage-gated Na + channel, as it exists
in excitable cells, as an example of a receptor with multiple binding sites for different types of
toxins. Occluders, activators and stabilizers are considered as modes for toxins binding to and
acting directly on the ion channel. Saxitoxin acts by inhibiting the temporary permeability to Na +
ions, and this has made a considerable contribution to the hypothesis that the Na + and K + ions
move independently through the cell membrane by separate channels and not by a single
common channel (Steidinger and Baden, 1984). At the molecular level all PSP toxins are watersoluble
non depolarizing toxins (Catterall, 1980). The saxitoxin as guanidinium toxin is regarded
a "blocking" agent that reduces the number of conducting Na + channels by occupying some site
near the outer opening (Richie and Rogart, 1977). Saxitoxin binds to specific receptors in the
nerve membrane in a 1:1 stoichiometry with high affinity (K D = 2 nM) (Catterall, 1979). The potent
inhibition of ion flux is not due to a plugging phenomenon but is rather the result of a lid on the
sodium channel, occupying a flat arrangement bound to the anionic surface of the membrane
(Kao and Walker, 1982) (Fig. 21). The recent experiments suggest that this action is not
independent of the presence of other toxins (Strichartz et al., 1987). So channels modified by
lipophylic toxins have to be altered in respect to STX also.
7.2.1.10 Therapeutical notes
In cases where humans eat saxitoxin-contaminated shellfish, symptoms appear within
minutes of ingestion, while death can occur anywhere from 1-12 hr later (Kao, 1966; Halstead,
1978). This should give sufficient time to intervene with an injection of antiserum.