Batrachotoxinins toxicity

Batrachotoxin, not unexpectedly in view of its use as a dart poison by South American Indians, is an extremely toxic substance. The LDjq on subcutaneous injection in mice is about 40 ng. Homobatrachotoxin is only slightly less toxic, while batrachotoxinin A is 500-fold less toxic. The nature of the ester function at the 20a position is of critical importance to toxicity. Thus, the 20a-benzoate of batrachotoxinin A is fully as toxic as batrachotoxin, whereas the 20a-4-bromobenzoate has very low toxicity. For a summary of the toxicides of natural and synthetic batrachotoxins, see Ref. 5. 

The most famous of the many alkaloids isolated so far is without any doubt batrachotoxin and its derivatives. Batrachotoxin has a LD50 of 2 ug per kg body weight (mouse, i.m.), thus being the most toxic nonprotein substance at all. Because of its special pharmacologic activity to keep open irreversably the sodium channels of nerve cells it has become an important tool in the studies of sodium channels. Chemically the batrachotoxins are esters of a 20-hydroxy steroid, batrachotoxinin A, with different pyrrol carboxylic acids. Although the activities of the different batrachotoxins is qualitatively the same, it differs quantitatively according to the acid part of the molecule (refs. 14, 15). 

A knowledge of the structure of batrachotoxinin A led to a re-evaluation of the spectral properties of the much more toxic batrachotoxin and homobatrachotoxin. It soon became apparent that the ultraviolet absorption peaks (A.max 234, 264 nm), the infrared red absorption band at 1690 cm " S and additional nuclear magnetic resonance absorption peaks in... 

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