PHARMACOLOGICALLY ACTIVE COMPOUNDS FROM AMPHIBIANS AND OTHER NATURAL SOURCES

天然产物提供了广泛的生物活性制剂，很多

Natural products provide a wide range of biologically active agents, many of which have unique profiles of pharmacological activity and therapeutic potential. Over three hundred alkaloids have been identified in extracts from amphibian skins. These included batrachotoxins, which are potent activators of sodium channels, histrionicotoxins, which are noncompetitive blockers of nicotinic receptor channel complexes and of potassium channels, and pumiliotoxins, which have myotonic and cardiotonic activity due to inhibitory effects on closing of sodium channels. Further alkaloids included 2,5-disubstituted decahydroquinolines, 5,8- disubstituted indolizidines, 1,4-disubstituted quinolizidines, 3,5- disubstituted pyrrolizidines, pumiliotoxins, homopumiliotoxins and allopumiliotoxins, and tricyclic alkaloids, including pyrrolizidine oximes, cyclopenta[b]quinolizidines, cocinellines, and the potent nonopioid analgetic epibatidine. Homobatrachotoxin has been discovered in feathers, skin and muscle of a New Guinean bird. Characterization of alkaloids in non-dendrobatid amphibians indicated that the biosynthetic pathways to certain dendrobatid alkaloids have evolved separately in one lineage (genus) of amphibians from the families Bufonidae, Myobatrachidae and Ranidae and in a lineage leading to four genera in the family Dendrobatidae. The lack of alkaloid production in captive-raised dendrobatid frogs remains an enigma. Synthetic routes to epibatidine and to the pyrrolizidine oximes have been developed. There was no correlation between inhibition of batrachotoxin binding and anticonvulsant activity for a series of analogs of carbetapentane.individuals devoid of renal disease was also undertaken.