Histrionicotoxins are a group of related toxins found in the skin of poison frogs from the Dendrobatidae family, notably Dendrobates histrionicus. 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 receptor

Nicotinic acetylcholine receptor

Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...

s, binding to a regulatory site

Regulatory site

A regulatory site is a site on an allosteric protein to which a modulator molecule binds. A ligand-binding site on a receptor or enzyme distinct from the active site. Allosteric modulators alter enzyme activity by binding to the regulatory site. Also known as an "allosteric site"....

 on the delta subunit of the ion channel complex. They also have some affinity for sodium and potassium channel

Potassium channel

In the field of cell biology, potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. They form potassium-selective pores that span cell membranes...

s, 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.