POISONS OF TOADS 155 



dicates an empirical I'oiiuuhi of C34H54O2. It probably is the cause 

 of the milky appearance of the dermal secretion. Bufotahn seems to 

 be C34H46O10, is acid in reaction, soluble in chloroform and alcohol, 

 but not in petroleum ether. Subcutaneous injection of 2.G mg. bufo- 

 talin killed a dog (weighing 4 kg.) in four to five hours; given by 

 mouth it causes much vomiting and diarrhea, so that large doses are 

 not fatal. It causes much local irritation when applied to mucous 

 membranes, but produces no marked change at the site of injection. 

 The effects on the circulation resemble in all respects those of the digi- 

 talis group; bufonin acting similarly but much weaker than bufotalin. 

 Bufotalin seems to be derived from bufonin by oxidation, and the latter 

 is quite similar to cholesterol, apparently having the following formula: 

 HO-H26C17-C17H26-OH. An important consideration is that Faust 

 has also isolated from the venom of cobra and crotalus, poisons which 

 seem related to these toad poisons, the cobra poison being assigned an 

 empirical formula of Ci7H260io, and the crotalus poison C34H54O21. 

 Fiihner^^ considers bufotalin to be more closely related to the saponins. 

 Phisalix and Betrand^- have found poison in the blood of toads 

 similar to that of the glands. The hemolytic property observed by 

 Pugliese^^ may be due to the acidity of the dermal secretion. The 

 poisons of chfferent species seem to be quite the same in all (Faust). 

 From the dermalsecretion of the large tropical toad, Bufo agiia, Abel 

 and Macht^* have isolated two distinct active substances; one identical 

 with epinephrine, which constitutes nearly seven per cent, of the crude 

 venom; the other, which makes up 36 per cent., is called hvfagin, has 

 a composition indicated by the formula C1SH24O0, and therefore is 

 presumably related to the rest of this group which arises from choles- 

 terol. In physiological action bufagin resembles digitalis, and it is ex- 

 tremely active. The toad is relatively immune to bufagin, but not 

 at all to the epinephrine. A Chinese drug derived from toad skins has 

 been found to contain similar ingredients (Shimizu^^), as well as a 

 substance resembling picrotoxin in action. 



Salamanders also produce poisonous secretions in their dermal glands, which 

 have been studied especially by Faust,^" and earlier by Zalesky,^^ who isolated an 

 organic base which he named samandarin. Faust describes samandarin as first 

 stimulating and then paralyzing the automatic centers in the medulla. The 

 poison resembles the alkaloids, having the formula C26H40N2O, and produces 

 death in doses of 0.7-0.9 mg. per kilo (dogs) with respiratory failure. Immuniza- 

 tion of rabbits was practically impossible. A second alkaloid, samandaridin 

 (C-.uH.nXO) is also present in even greater quantities than the samandarin, and 

 differs only in being weaker. 



Frogs also have similar poisons in their skins, extracts of Rana esculenta skin 



91 Arch. exp. Path. u. Pharm., 1910 (63), 374. 



9- Arch. d. physiol. norm, et path., 1893 (5), 511. 



9' Archivo di farm. e. terap., 1894 (2), 321; Arch, ital de Biol., 1895 (22), 79. 



"Jour. Amer. Med. Assoc. 1911 (5lJ), 1531; Jour, of Pharm., 1912 (3), 319. 



95 Jour. Pharmacol., 1916 (8), 347. 



9«Arch. e.xper. Path. u. Pharm. 1898 (41), 229 (literature); 1900 (43), 84. 



9' Hoppe-Seyler's Med. Chem. Untersuch., 1866, p. 85. 



