MARINE TOXINS AND VENOMOUS AND POISONOUS MARINE ANIMALS
323
muscle (reducing its excitability), and on the contractile force of the
heart. It was said to have no cholinesterase activity.
In 1942, Kuros presented evidence which appeared to indicate that
tetrodotoxin has little effect on the acetylcholine contracture of the
perfused gastrocnemius muscle of the toad. He proposed that the
toxin had no curariform-like activity. Subsequently, Furukawa et al.
(1969) concluded, on the basis of their studies on the frog sartorius
nerve-muscle preparation, that while tetrodotoxin has a potent
narcotic effect on nerve and muscle it does not depolarize them. The
poison did not suppress the sensitivity of the end-plate to acetylcholine, even at concentrations greater than those necessary for the
narcosis of the nerve and muscle. All of the above studies were conducted with relatively crude preparations of the toxin ; nevertheless,
some of the findings are supported by more recent investigations.
When the toxin is ingested by mammals, lethargy, muscular
weakness and incoordination develop rapidly. Ataxia occurs and paralysis is observed, first in the hind limbs and later in the fore limbs.
Retching and vomiting are often severe. Deep reflexes are lost and
respirations become labored. Cyanosis may be apparent and convulsions sometimes occur. In cats the oral LD,, of the toxin is in excess
of 0.20 mg/kg body weight. The minimum lethal dose in mice is
approximately 8.0 pg/kg.
Murtha and colleagues (1958) extracted the toxin from three
species of Sphoeroides with acidified methanol, purified by precipitation
with acetone, by adsorption on CS-101 and XE-89 resins and by final
precipitation with A-20 resin and solid sodium carbonate. The product
was assayed as a crystalline hydrochloride, and in cats found to have
an intraperitoneal LD,, of less than 10 pg/kg body weight. When
5 pg/kg was injected intravenously into cats, there was a precipitous
fall in blood pressure and rapid cessation of respirations. In bilaterally
vagotomized cats with transected cervical cords, similar changes were
seen. The electrocardiograms were unremarkable, except for decreases
in heart rate. However, studies on the heart in open-chest dogs showed
that the toxin had a deleterious effect on contractile force. Li (1963)
was unable to demonstrate a change in cardiac output following injection of his preparation of the toxin. He suggested that the hypotensive crisis was due exclusively to changes in the peripheral blood
vessels.
Murtha and colleagues (1958) also found that the toxin had a more
depressant effect on respiration when it was given through the carotid
artery than when given through a vein. They interpreted this fact
to indicate that the poison had a direct effect on the brain. The finding
R 2
323
muscle (reducing its excitability), and on the contractile force of the
heart. It was said to have no cholinesterase activity.
In 1942, Kuros presented evidence which appeared to indicate that
tetrodotoxin has little effect on the acetylcholine contracture of the
perfused gastrocnemius muscle of the toad. He proposed that the
toxin had no curariform-like activity. Subsequently, Furukawa et al.
(1969) concluded, on the basis of their studies on the frog sartorius
nerve-muscle preparation, that while tetrodotoxin has a potent
narcotic effect on nerve and muscle it does not depolarize them. The
poison did not suppress the sensitivity of the end-plate to acetylcholine, even at concentrations greater than those necessary for the
narcosis of the nerve and muscle. All of the above studies were conducted with relatively crude preparations of the toxin ; nevertheless,
some of the findings are supported by more recent investigations.
When the toxin is ingested by mammals, lethargy, muscular
weakness and incoordination develop rapidly. Ataxia occurs and paralysis is observed, first in the hind limbs and later in the fore limbs.
Retching and vomiting are often severe. Deep reflexes are lost and
respirations become labored. Cyanosis may be apparent and convulsions sometimes occur. In cats the oral LD,, of the toxin is in excess
of 0.20 mg/kg body weight. The minimum lethal dose in mice is
approximately 8.0 pg/kg.
Murtha and colleagues (1958) extracted the toxin from three
species of Sphoeroides with acidified methanol, purified by precipitation
with acetone, by adsorption on CS-101 and XE-89 resins and by final
precipitation with A-20 resin and solid sodium carbonate. The product
was assayed as a crystalline hydrochloride, and in cats found to have
an intraperitoneal LD,, of less than 10 pg/kg body weight. When
5 pg/kg was injected intravenously into cats, there was a precipitous
fall in blood pressure and rapid cessation of respirations. In bilaterally
vagotomized cats with transected cervical cords, similar changes were
seen. The electrocardiograms were unremarkable, except for decreases
in heart rate. However, studies on the heart in open-chest dogs showed
that the toxin had a deleterious effect on contractile force. Li (1963)
was unable to demonstrate a change in cardiac output following injection of his preparation of the toxin. He suggested that the hypotensive crisis was due exclusively to changes in the peripheral blood
vessels.
Murtha and colleagues (1958) also found that the toxin had a more
depressant effect on respiration when it was given through the carotid
artery than when given through a vein. They interpreted this fact
to indicate that the poison had a direct effect on the brain. The finding
R 2