Batrachotoxin, toxicity

Dumbacher, J. P., Spande, T. F., and Daly, J. W. (2000). Batrachotoxin alkaloids from passerine birds a second toxic bird genus Ifrita kowaldi) from New Guinea. Proceedings of the National Academy of Sciences of the USA 97,12970-12975. 

Several major types of animals that produce poisonous substances have been considered so far in this chapter. With the exception of birds, all classes of the animal kingdom contain members that produce toxic substances. It has now been demonstrated that there are even birds that are toxic. It is believed that such birds do not produce toxins but accumulate toxic alkaloids, including andromedotoxin, batrachotoxins, and cantheridin, from their diets and deposit these poisonous materials in their skin and feathers.19 Toxic animals not covered so far in this chapter are summarized here. 

Since some alkaloids exhibit great mammalian toxicity (e.g., batrachotoxin, samandarine), it is obvious that these compounds are capable of initiating severe biochemical and physiological lesions. However, it should not be overlooked that toxicological evaluations of most alkaloids have been implemented by in vitro studies in which the alkaloids have been introduced subcutaneously. On the other hand, in nature, in the absence of a venom apparatus, these compounds would be... 

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 pharmacology of batrachotoxins that underlies their high toxicity is the result of a specific high-affinity interaction of batrachotoxin with a... 

More recent studies have identified the most potent toxin produced by the frog as batrachotoxin (although it is one of about a hundred toxins). This is one of the most toxic substances known—five times more potent than tetrodotoxin, the toxin found in puffer fish (see pp. 252-3)—and a dose of 200 pg would be lethal for a human. Interestingly, tetrodotoxin is also found in the Californian newt. Batrachotoxin is secreted through the skin when the animal is stressed, and so when animals hck or bite the frog they are exposed to the toxin, which causes death by stopping the heart beating. 

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). 

Tetradotoxin is a potent neurotoxin isoiated from the ovaries and liver of many species of Tetradodontidae, especiaiiy the Japanese fugu (or puffer fish). Saxitoxin is a mussel or clam poison produced by certain marine dinoflagellates, Gonyaulax catenella or G. tamarensis, the consumption of which cause the mussels or clams to become poisonous. These poisonous shellfish were connected to a toxic red tide environmental condition on the coastal region of California in early 1970. Batrachotoxin is a cardiotoxic and neurotoxic steroid isolated originally from the poison dart frog, Phyllobates terribilis. It is a lipid soluble neurotoxin that is at least 10-fold more toxic than tetradotoxin. 

The synthesis of the steroidal amine (51) has been reported. Compound (51) is structurally related to the extremely toxic alkaloid batrachotoxin (52), isolated from the skin of the Columbian arrow-poison frog, Phyllobates aurotaenia. The isolation of tomentomin (53) from leaves of Marsdenia tomentosa is the subject of a recent patent. ... 

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