Phyllobates aurotaenia

Very rapid-acting paralytic neurotoxin that binds to sodium channels of nerve and muscle cells depolarizing neurons by increasing the sodium channel permeability. It is obtained from South American poison-dart frogs (Phyllobates aurotaenia, Phyllobates terribilis). It is insoluble in water but soluble in hydrocarbons and other nonpolar solvents. The dried toxin can remain active for at least a year. However, it is relatively nonpersistent in the environment. 

The batrachotoxins were the first class of unique alkaloids to be characterized from skin extracts of frogs of the family Dendrobatidae (see ref. 23 for a review of amphibian alkaloids). Batrachotoxin was detected in only five species of dendrobatid frogs and these frogs were then classified as the monophyletic genus Phyllobates, based in part on the presence of batrachotoxins (24). However, levels of batrachotoxins differ considerably, with the Colombian Phyllobates terribilis containing nearly 1 mg of batrachotoxins per frog, while the somewhat smaller Phyllobates bicolor and Phyllobates aurotaenia, also from the rain forests of the Pacific versant in Colombia, contain 10-fold lower skin levels (8). The two... 

Dendrobatidae Phyllobates aurotaenia Cardiotoxin Neuro toxin Batrachotoxin Homobatrachotoxin... 

Batrachotoxin A (III), just one of many steroidal alkaloids, is one of the most lethal substances known (LD50 = 2/xg/kg subcutaneously in mice). It is found in the skin secretions of the brightly colored tropical frog Phyllobates aurotaenia and is used by Colombian Indians to prepare poison darts. 

Considerable difficulties had to be overcome in the isolation of four major highly cardiotoxic steroidal alkaloids from the skin secretions of the Colombian arrow-poison frog Phyllobates aurotaenia. The very labile pseudobatrachotoxin, whose... 

The synthesis of batrachotoxin (439), the steroidal alkaloid from the poison arrow frog Phyllobates aurotaenia, has continued to attract attention. The partial synthesis of various 3) -methoxy-3a,9a-oxido-7a-hydroxy-lla-acetoxy-5/ -steroids has been reported. In particular (Scheme 24), the -double bond... 

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. ... 

Batrachotoxin Phyllobates aurotaenia and terribilis (Columbian frog)... 

Batrachotoxins. Highly poisonous "steroid alkaloids (see table) isolated from the skin of the Colombian frogs Phyllobates aurotaenia, P. terribilis, P. bicolor, P. vittatus, and P. lugubris. B. (as skin preparations) are used as arrow poisons. 

Phyllobates aurotaenia inhabits South America, where it is known as kokoi. A toxic material is secreted from the skin, and the secretion is utilized as an arrow poison. The toxic material was studied at the National Institutes of Health (U.S.A.), and batrachotoxin was reported as the main toxic component in 1969 [1]. Although there are no reports on the biosynthesis of this compound, it appears that in this alkaloid the nitrogen atom was incorporated into a steroid skeleton. A nitrogen atom has also been introduced into the side-chain moiety in the form of a pyrrole-3-carboxylic acid derivative. The LD50 value of batrachotoxin is 2 xg/kg (mouse/subcutaneous injection). 

The structure of batrachotoxinin A (26), a component of an arrow poison from the skin of the frog Phyllobates aurotaenia, has been elucidated by X-ray crystallography52. 

Histrionicotoxins. Another poison frog, Dendrobates histrionicus occurred sympatric with the poison-dart frog Phyllobates aurotaenia in Western Colombia. Preliminary studies based primarily on mass spectrometry of compounds isolated by thin-layer chromatography, indicated the presence of another class of relatively simple alkaloids in extracts from a few specimens of this species. Three major alkaloids were later isolated from skin extracts of a population of Dendrobates histrionicus from southwestern Colombia and the structures of two of these were reported in 1971 (81). The compounds were unique spiropiperidine alkaloids with remarkable acetylenic and allenic centers of unsaturation in the side chain substituents. The parent compound was named histrionicotoxin after the specific name of the frog Dendrobates histrionicus from which it was first isolated. A number of histrionicotoxins were subsequently isolated and structurally defined 86, 253). Like pumiliotoxin C, the histrionicotoxins exhibit relatively low toxicity to mammals. 

Biosynthetically, little is known of the origin of these alkaloids. In a preliminary study, radioactive acetate and mevalonate were incorporated into skin steroids of frogs, while incorporation of these potential precursors into skin alkaloids was not detected (750). Neither radioactive cholesterol nor serine was significantly incorporated into the batrachotoxins. Three species, Phyllobates aurotaenia, Dendrobates pumilio and Dendrobates auratus were used in these exploratory biosynthetic studies. 

Albuquerque, E. X., J. E. Warnick, F. M. Sansone, and J. Daly The pharmacology of batrachotoxin. V. A comparative study of membrane properties and the effects of batrachotoxin on sartorius muscles of the frogs Phyllobates aurotaenia and Rana pipiens. J. Pharmacol. Exp. Therapeut. 184, 315—329 (1973). 

Tokuyama, T., j. Daly, and B. Witkop The structure of batrachotoxin, a steroidal alkaloid from the Colombian arrow poison frog, Phyllobates aurotaenia, and partial synthesis of batrachotoxin and its analogs and homologs. J. Amer. Chem. Soc. 91, 3931—3938 (1969). 

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