Botulism and Picrotoxin

Abstract

Two phases are differentiated in botulinal intoxication: (1) a period of stimulation and (2) of respiratory depression. Experiments with picrotoxin point to reciprocal potentiation during the phase of botulinal stimulation and antagonism during the phase of depression.

The botulinal toxin (type A) in these experiments was prepared and supplied by the National Institute of Health in Washington. Its potency was expressed in terms of an intravenous mouse MLD, one unit being 0.00005 cc, the smallest amount that would kill a 17 to 20 g mouse when injected intravenously.

These experiments were performed on healthy stock rabbits ranging in weights from 1.45 to 1.85 kg.

Injected into the marginal ear vein 10,000 U (0.5 cc) of the toxin caused death (100%) within 13 hours average time. Three mg of picrotoxin intravenously administered is surely convulsant and frequently lethal; 2 mg is usually convulsant but non-lethal; while 1 mg is never lethal, rarely convulsant but regularly hyper-stimulating to normal rabbits within this weight-range. However, when within the first hour following the injection of botulinal toxin, 3 mg, 2 mg, or 1 mg of picrotoxin was injected into the vein or even the muscle all the animals died within the first 2 hours with severe convulsions. But when an interval of 3 to 5 hours was allowed to elapse between the time of injection of toxin and picrotoxin with the picrotoxin divided into 0.1 mg doses each hour, sub-cutaneously, the life span was extended from an average of 13 (controls) to 23 hours. (Table I-a.)

Intraäbdominally, 20,000 U, 40,000 U, and 60,000 U, each of botulinal toxin was 100% lethal in 5 hours (average time). When administered by this route and in these amounts there began to appear signs of intoxication between the second and the third hour.