Alkaloids from frog skins: selective probes for ion channels and nicotinic receptors

ABSTRACT

Amphibian skin has provided a wide range of biologically active alkaloids, many of wich have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified and structures of over a dozen different classes of alkaloids have been elucidated. These iclude the batrachotoxins, wich were shown to be potent and selective activators and ligands for sodium channels, the histrionicotoxins, wich were shoen to be potent non-competitive blockers and ligands for nicotine receptor channel complexes, the pumiliotoxins and related allo-and homo-pumiliotoxins, wich were shown to have myotonic and cardiotonic activity due to effects on sodium channels, and epibatidine, wich was shown to have potent antinociceptive activity due to selective agonist activity at nicotinic receptors. These alkaloids are known in nature only in amphibian skin, except for homobatrachotoxin, wich was recently identified in feathers and skin of a bird. Further classes of alkaloids from amphibian skin include monocyclic pyrrolidines and piperidines, bicyclic decahydroquinolines, pyrrolizidines, and quinolozidines and tricyclic gephyrotoxins, pyrrolizidine oximes, etc..