Discovery of Batrachotoxin: The Launch of the Frog Alkaloid Program at NIH

Abstract

The determination of the structures of the batrachotoxins (BTXs), extremely toxic steroidal alkaloids found in the skins of the dart-poison frogs of the genus Phyllobates from Colombia in the 1960s is reviewed. The BTXs function by locking open sodium-ion channels of nerve and muscle, thereby depolarizing them. The structures and pharmacology of the BTXs were determined by a team led by John W. Daly. This research started a 40 year long study of alkaloids from frog skin, whereby John and his team identified and/or characterized more than 800 such alkaloids. The source of the BTXs, not synthesized but sequestered from diet by the frogs, is briefly discussed, in the context of the occurrence of BTXs in birds of Papua New Guinea and in a small melyrid beetle found there. Emphasized is the critical importance of maintaining and safe-guarding the large collection of frog-skin extracts and data accumulated since.