THE TOXICITY OF d‐TUBOCURARINE TO RATS

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Abstract
SUMMARY: Female Wistar rats were found to be more susceptible to the lethal effect of d‐tubocurarine than were male rats of the same strain and age. The LD50 of d‐tubocurarine administered intraperitoneally was estimated as 0·256 mg./kg. body weight for female rats and 0·328 mg./kg. for male rats.Sedative doses of sodium amytal were found to protect against the lethal effect of relatively large single doses of d‐tubocurarine. However, doses of sodium amytal repeated over several days had the opposite effect and increased the susceptibility of rats to small doses of d‐tubocurarine. The effect of amytal appears not to be due to sedation.Rats given several doses of d‐tubocurarine at or above the LD50 did not show any biochemical or histological evidence of liver damage. Long courses of frequent injections of d‐tubocurarine at lower dose rates than the LD50 did not result in any detectable enzymological dysfunction of, or histopathological change in, the liver. It is concluded that although d‐tubocurarine is potentially hepatotoxic by virtue of its effect in vitro on liver mitochondria it is such a highly specific neuromuscular blocking agent at such low dose rates that, under usual conditions, animals die from neuromuscular paralysis before the alkaloid enters the liver in sufficient quantities to cause damage.