146 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 



The venoms of Enhydrina and Distira, two marine snakes, contain very 

 little of the haemolytic principles, but are many times more toxic than that of 

 the most dreaded land snake, the cobra. One minimal lethal dose of the 

 venom of Enhydrina can destroy about 2~or part of the blood of the animal 

 injected with this venom. (Rogers.) 



The resistance of the haemolysins is shown to be much weaker than that of 

 the neurotoxins against peptic digestion (Flexner and Noguchi). 



So much for the biological isolation of the neurotoxins from the haemolysins. 



The next phase of this subject is of its chemical isolation, which was first 

 accomplished by Kyes and later confirmed by von Dungern and Coca. Kyes 

 succeeded in isolating venom lecithid by shaking an aqueous solution of 

 venom with a chloroform solution of lecithin. The venom lecithid is exclu- 

 sively haemolytic, but not at all toxic. On examining the venom solution 

 from which the venom lecithid has been separated by centrifugalization, Kyes 

 found that the original toxicity of cobra venom was left in the aqueous portion 

 in undiminished quantity. 1 Thus the hsemolytic and neurotoxic principles 

 have been completely separated. The injection of the venom lecithid in a 

 large quantity does not kill the animal. On the other hand, the remaining 

 venom solution is no longer haemolytic, but still highly neurotoxic. Von Dun- 

 gern and Coca prepared the lecithid by the same method, but they once 

 found that the venom solution still contained a certain amount of haemolysins, 

 while another time the removal of haemolysins was complete. 



Morgenroth prepared venom lecithid by a slightly modified method, in 

 which methyl alcohol was substituted for chloroform. This preparation 

 was not only haemolytic, but also neurotoxic to a certain extent. This 

 apparent difference from the result ascertained by Kyes was later explained 

 by him to be due to the adherence of the neurotoxic principles to the precipi- 

 tated lecithid. Kyes assumed that weak alcohol contains enough water to hold 

 the neurotoxins in solution, and at the moment of the precipitation of the 

 lecithid with ether the neurotoxins are mechanically carried down. 



Faust finally isolated an active substance, the ophiotoxin, from cobra venom 

 by pure chemical processes. 2 



Ophiotoxin is obtained from the non-coagulable, non-dialyzable portion 

 of cobra venom by means of 10 per cent metaphosphoric acid, which precipi- 

 tates all the biuret-giving substances. Now, the filtrate contains only protein- 

 free active substance of the venom, and by adding alcohol it is precipitated 

 out. It is an amorphous, somewhat yellowish powder, soluble in water, and 

 forms foam by shaking the solution. It is slightly acid, non-dialyzable, and 

 nitrogen-free; it has the formula of C 17 H 26 O 10 . According to Faust this sub- 

 stance belongs to the same group as sapotoxins. Its action is nearly 5 times 

 stronger than the native venom, but with a great tendency to become inactive 



1 Jacoby made a comparative study of the effects of the isolated neurotoxin and the raw venom of cobra, 



and found that there is no essential difference in their pharmacological actions on the nervous 

 system. Salkowski-Festschrift, 1904, Berlin. 



2 For the details see " Physical and chemical properties of venom," page 90. 



