Thirty years of discovering arthropod alkaloids in amphibian skin

Amphibian skin has provided a wide range of biologically active alkaloids. During the past 30 years, over 400 alkaloids of over 20 structural classes have been detected. These include the batrachotoxins, which are potent and selective activators of sodium channels, the histrionicotoxins, which are potent noncompetitive blockers of nicotinic receptor-gated channels, the pumiliotoxins and related allo- and homo-pumiliotoxins, which have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, which has potent antinociceptive activity due to agonist activity at nicotinic receptors. Further classes of alkaloids from amphibian skin include pyrrolidines and piperidines, decahydroquinolines, pyrrolizidines, various indolizidines, quinolizidines, and tricyclic gephyrotoxins, pyrrolizidine oximes, pseudophrynamines, coccinellines, and cyclopentaquinolizidines. Most alkaloids of amphibian skin appear to be sequestered from dietary arthropods. The source of the batrachotoxins, histrionicotoxins, pumiliotoxins, epibatidine, and certain izidines are unknown.