Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the Dendrobatidae family, notably Oophaga histrionica. It is likely that as with other poison frog alkaloids, histrionicotoxins are not manufactured by the amphibians, but absorbed from insects in their diet and stored in glands in their skin.
Histrionicotoxins are less powerful toxins compared to many of the other alkaloids found in poison frogs; however, they have an unusual chemical structure and a distinct mechanism of action, acting as a potent non-competitive antagonists of nicotinic acetylcholine receptors, binding to a regulatory site on the delta subunit of the ion channel complex. They also have some affinity for sodium and potassium channels, although they are much less potent for these targets. The synthesis of histrionicotoxins and various homologues is synthetically challenging and has been the subject of many different attempts.
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