Biodiversity of Alkaloids in Amphibian Skin: A Dietary Arthropod Source

Over four hundred alkaloids in amphibian skin have been detected and structures from twenty different classes have been elucidated. These include batrachotoxins, histrionicotoxins, pumiliotoxins, epibatidine, pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, quinolizidines and tricyclic gephyrotoxins, pyrrolizidine oximes, pseudophrynamines, coccinellines and cyclopentaquinolizidines. The alkaloids of amphibian skin are not synthesized by the amphibians, but instead are accumulated unchanged from dietary sources. Pyrrolidines, piperidines, decahydroquinolines, pyrrolizidines, indolizidines, and quinolizidines appear likely to be derived from ants, the coccinellines from beetles, and the pyrrolizidine oximes from millipedes. The origins of the batrachotoxins, histrionicotoxins, pumiliotoxins and epibatidine are of particular interest in view of their remarkable biological activity. INTRODUCTION Amphibian skin contains a remarkable spectrum of biologically active compounds, including biogenic amines, peptides, proteins, bufadienolides, tetrodotoxins and lipophilic alkaloids (ref.1). The lipophilic alkaloids include the samandarines and an incredible array of piperidine-based, pyrrolidine-based, and steroidal alkaloids. Such an array of over four hundred new alkaloids has been detected in skin extracts from four genera of dendrobatid frogs of New World tropics, the bufonid genus Melanophryniscus of Southeastern South America, the mantelline genus Mantella of Madagascar, and the myobatrachid genus Pseudophryne of Australia (refs. 2,3). Skin extracts from 71 other genera encompassing 11 anuran families have not contained alkaloids. ALKALOIDS FROM ANURAN SKIN Over 20 major structural alkaloid classes, several of which may co-occur in a single frog, have been detected in anuran skin. Such alkaloids include the batrachotoxins (sodium channel activators), the histrionicotoxins (noncompetitive blockers of nicotinic channels), the pumiliotoxin, allopumiliotoxin, and homopumiliotoxin group (positive modulators of sodium