Acute Lethality of the Amphetamines in Dogs and Its Antagonism by Curare,

Summary

The acute lethal dose of amphetamine, dextroamphetamine and meth-amphetamine was determined in dogs for both the oral and intravenous routes. The LD50 of amphetamine was 23.3 mg/kg orally and 5.9 mg/kg intravenously. Dextroamphetamine and methamphetamine were both found to be twice as toxic as amphetamine. It was estimated that the LD50 of amphetamine in man may be as low as 4 mg/kg orally and one mg/kg intravenously. These estimates are supported by clinical experience with fatal amphetamine poisoning and are thought to be more realistic than the frequently quoted LD50 for man of 20-25 mg/kg. Additional studies were performed in un-anesthetized dogs curarized with d-tubocura-rine, after which “lethal” doses of amphetamine sulfate were given intravenously. Not only did these animals fail to demonstrate the hyperthermic response usually associated with amphetamine, but they were afforded protection from the lethal effect as well. Amphetamine sulfate administered intravenously in doses greater than 16 times the LD50 could be given with relative impunity to the curarized dog. The mechanism by which this protection is afforded has not yet been established.