30 



accurate as might be desired and show only a fair degree of uniformity. 

 Figures for the amounts found in the dried leaf varied from 0.57% 

 to 0.66%; bulb, 0.188% to 0.57%; flower, 1.07% to 1.35%; root, 

 0.306% to 0.32%. 



A quantity of material was prepared and submitted to Dr. Phillip 

 Mitchell and Mr. Geo. Smith for toxicological experiments. The mate- 

 rial used in these experiments was not the more highly purified crystal- 

 lized alkaloid which was reported on later. It was found that when 

 injected intraperitoneally a quantity between 4.6 mg. and 5.1 mg. would 

 produce death in a guinea pig. When administered by mouth a com- 

 paratively large quantity was required for fatal effects in the guinea 

 pig. The larger amount necessary was partially accounted for by 

 the fact that' the material caused vomiting. In the guinea pig the 

 effects of the material appeared to be the same after subcutaneous or 

 intraperitoneal injection or after feeding. 



The mixed alkaloids cause vaso-dilatation and apparently affect the 

 cardio-inhibitory center, slowing the heart action. Respiration was 

 slowed. After doses approaching the fatal quantity the heart-beat 

 becomes rapid and irregular and there is convulsive respiration. In 

 dogs the fatal dose given intravenously stopped the heart before 

 respiration ceased. When either injected or fed, it had a powerful 

 action both as a purgative and an emetic. 



Later, in the Wyoming experiments, a more highly purified alkaloid 

 was obtained which could be crystallized from alcohol and benzene. 

 The crystalline material from benzene melted at 200-210 and was 

 found to have the formula C 39 H 63 N0 10 . The physiological action was 

 tested by Dr. Phillip Mitchell, who reported its effects to be different 

 from those found for the mixed alkaloids. Its behavior was in general 

 much like the alkaloid veratrine and it required comparatively large 

 quantities to kill guinea pigs. Unlike the mixed alkaloids it had no 

 noteworthy effect on the heart and apparently caused complete loss 

 of muscular control. 



In 1918 Dr. C. A. Jacobson of the Nevada Station reported obtaining 

 a new alkaloidal product from Zygadenus paniculatus. This alkaloidal 

 product was designated by him as "Z-alkaloid." The crude alkaloid was 

 prepared by extracting the ground and dried plant with 95% alcohol, 

 concentrating the extract to a sirup and pouring into a dilute solution 

 of tartaric acid to remove resins and other impurities. The clear acid 

 solution was further purified by extraction with ether ; and the crude 

 alkaloid was precipitated by the addition of sodium carbonate. The 

 precipitate was an amorphous sticky mass poisonous to rabbits. The 

 liquid containing the precipitated solid matter was extracted with 

 ether. It was found that if the ether was completely removed on the 

 water bath, the material would then undergo violent effervescence and 

 the resulting product would no longer be poisonous. If, however, the 

 last of the ether was allowed to evaporate in the air at ordinary tem- 

 peratures no effervescence took place and the resulting material 

 retained its potency. Further purification was effected by re-solution 

 in tartaric acid, removal of impurities with ether, neutralization and 

 extraction with ether and chloroform. 



The more purified Z-alkaloid had an increased toxicity, about 0.35 

 gram being found to be lethal for rabbits when administered by mouth. 



